Variant 10-60196628-GAA-GAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_020987.5(ANK3):c.1690-4_1690-3insTTTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000535 in 1,260,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

ANK3
NM_020987.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.469

Variant links:

Genes affected

ANK3 (HGNC:494): (ankyrin 3) Ankyrins are a family of proteins that are believed to link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact, and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 3 is an immunologically distinct gene product from ankyrins 1 and 2, and was originally found at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

ANK3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 10-60196628-G-GAAAA is Benign according to our data. Variant chr10-60196628-G-GAAAA is described in ClinVar as [Likely_benign]. Clinvar id is 3037817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000563 (635/1127110) while in subpopulation AFR AF= 0.0112 (291/26030). AF 95% confidence interval is 0.0101. There are 0 homozygotes in gnomad4_exome. There are 291 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ANK3	NM_020987.5 linkuse as main transcript	c.1690-4_1690-3insTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000280772.7
ANK3	NM_001204403.2 linkuse as main transcript	c.1672-4_1672-3insTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ANK3	NM_001204404.2 linkuse as main transcript	c.1639-4_1639-3insTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ANK3	NM_001320874.2 linkuse as main transcript	c.1690-4_1690-3insTTTT	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7 linkuse as main transcript	c.1690-4_1690-3insTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020987.5		Q12955-3

Frequencies

GnomAD3 genomes

AF:

0.000293

AC:

AN:

133084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000639

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000563

AC:

635

AN:

1127110

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

291

AN XY:

565044

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.000792

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.00439

Gnomad4 SAS exome

AF:

0.000370

Gnomad4 FIN exome

AF:

0.000107

Gnomad4 NFE exome

AF:

0.000105

Gnomad4 OTH exome

AF:

0.000868

GnomAD4 genome

AF:

0.000293

AC:

AN:

133118

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

AN XY:

63858

show subpopulations

Gnomad4 AFR

AF:

0.000969

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000641

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ANK3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 27, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over