NM_001378454.1(ALMS1):c.12284C>T (p.Pro4095Leu) AND Alstrom syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 9, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000668351.6

Allele description [Variation Report for NM_001378454.1(ALMS1):c.12284C>T (p.Pro4095Leu)]

NM_001378454.1(ALMS1):c.12284C>T (p.Pro4095Leu)

Genes:

ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]
LOC126806252:BRD4-independent group 4 enhancer GRCh37_chr2:73828496-73829695 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_001378454.1(ALMS1):c.12284C>T (p.Pro4095Leu)

HGVS:

NC_000002.12:g.73602354C>T
NG_011690.1:g.221602C>T
NM_001378454.1:c.12284C>TMANE SELECT
NM_015120.4:c.12287C>T
NP_001365383.1:p.Pro4095Leu
NP_055935.4:p.Pro4096Leu
LRG_741t1:c.12287C>T
LRG_741:g.221602C>T
LRG_741p1:p.Pro4096Leu
NC_000002.11:g.73829481C>T

Protein change:

P4095L

Links:

dbSNP: rs750502331

NCBI 1000 Genomes Browser:

rs750502331

Molecular consequence:

NM_001378454.1:c.12284C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015120.4:c.12287C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Alstrom syndrome (ALMS)
Synonyms:: Alstrom's syndrome
Identifiers:: MONDO: MONDO:0008763; MedGen: C0268425; Orphanet: 64; OMIM: 203800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000792933	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jul 24, 2017)	unknown	clinical testing	Citation Link,
SCV001416241	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002081410	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jun 30, 2021)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000792933

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jul 24, 2017)

unknown

clinical testing

Citation Link,

SCV001416241

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002081410

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Jun 30, 2021)

germline

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Counsyl, SCV000792933.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001416241.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 4096 of the ALMS1 protein (p.Pro4096Leu). This variant is present in population databases (rs750502331, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 552991). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV002081410.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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