rs10994359

chr10-60462349-T-C

Variant summary

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

The ENST00000373827.6(ANK3):c.96+152837A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 152,186 control chromosomes in the GnomAD database, including 1,131 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 0.085 (1131 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_001204403.2	c.96+152837A>G		intron_variant
ANK3	NM_001204404.2	c.63+110116A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000373827.6	c.96+152837A>G		intron_variant		1
ANK3	ENST00000503366.6	c.63+110116A>G		intron_variant		2
ANK3	ENST00000622427.4	c.63+110116A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0854 AC: 12986 AN: 152066 Hom.: 1126 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0746

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

GnomAD4 genome AF: 0.0854 AC: 12994 AN: 152186 Hom.: 1131 Cov.: 32 AF XY: 0.0956 AC XY: 7109 AN XY: 74378

Gnomad4 AFR AF: 0.0163

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0746 Hom.: 130

Bravo AF: 0.0861

Asia WGS AF: 0.246 AC: 852 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10994359; hg19: chr10-62222107;