rs958852

chr10-60562860-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000373827.6(ANK3):c.96+52326A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 151,628 control chromosomes in the GnomAD database, including 35,382 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35382 hom., cov: 33)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_001204403.2	c.96+52326A>T		intron_variant
ANK3	NM_001204404.2	c.63+9605A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000373827.6	c.96+52326A>T		intron_variant		1
ANK3	ENST00000503366.6	c.63+9605A>T		intron_variant		2
ANK3	ENST00000622427.4	c.63+9605A>T		intron_variant, NMD_transcript_variant		2
ANK3	ENST00000510382.1	n.101+52326A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102508 AN: 151510 Hom.: 35373 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.695

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.676 AC: 102562 AN: 151628 Hom.: 35382 Cov.: 33 AF XY: 0.685 AC XY: 50720 AN XY: 74064

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.812

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.695

Alfa AF: 0.687 Hom.: 4507

Bravo AF: 0.668

Asia WGS AF: 0.814 AC: 2815 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs958852; hg19: chr10-62322618;