NM_020987.5(ANK3):c.12368G>A (p.Arg4123His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 11, 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:: RCV001093304.26

Allele description [Variation Report for NM_020987.5(ANK3):c.12368G>A (p.Arg4123His)]

NM_020987.5(ANK3):c.12368G>A (p.Arg4123His)

Gene:

ANK3:ankyrin 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.2

Genomic location:

Preferred name:

NM_020987.5(ANK3):c.12368G>A (p.Arg4123His)

HGVS:

NC_000010.11:g.60064240C>T
NG_029917.1:g.674287G>A
NM_001149.4:c.1931G>A
NM_001204403.2:c.4511G>A
NM_001204404.2:c.4532G>A
NM_001320874.2:c.4529G>A
NM_020987.5:c.12368G>AMANE SELECT
NP_001140.2:p.Arg644His
NP_001191332.1:p.Arg1504His
NP_001191333.1:p.Arg1511His
NP_001307803.1:p.Arg1510His
NP_066267.2:p.Arg4123His
NC_000010.10:g.61823998C>T
NC_000010.10:g.61823998C>T

Protein change:

R1504H

Links:

dbSNP: rs780088040

NCBI 1000 Genomes Browser:

rs780088040

Molecular consequence:

NM_001149.4:c.1931G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001204403.2:c.4511G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001204404.2:c.4532G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320874.2:c.4529G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020987.5:c.12368G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001250221	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Nov 1, 2019)	germline	clinical testing	Citation Link,
SCV002148709	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33994118, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001250221

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Nov 1, 2019)

germline

clinical testing

Citation Link,

SCV002148709

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 11, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes.

Wang T, Zhang Y, Liu L, Wang Y, Chen H, Fan T, Li J, Xia K, Sun Z.

J Genet Genomics. 2021 Apr 20;48(4):312-323. doi: 10.1016/j.jgg.2021.03.002. Epub 2021 Apr 1.

PubMed [citation]

PMID:: 33994118

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 CeGaT Center for Human Genetics Tuebingen, SCV001250221.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002148709.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 872693). This missense change has been observed in individual(s) with ANK3-related conditions (PMID: 33994118). This variant is present in population databases (rs780088040, gnomAD 0.004%). This sequence change replaces arginine with histidine at codon 4123 of the ANK3 protein (p.Arg4123His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine.

#	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: Oct 20, 2024

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