rs10994415

chr10-60562276-T-Cchr10-60562276-T-G

Variant summary

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

The ENST00000373827.6(ANK3):c.96+52910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,284 control chromosomes in the GnomAD database, including 1,185 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 0.092 (1185 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_001204403.2	c.96+52910A>G		intron_variant
ANK3	NM_001204404.2	c.63+10189A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000373827.6	c.96+52910A>G		intron_variant		1
ANK3	ENST00000503366.6	c.63+10189A>G		intron_variant		2
ANK3	ENST00000622427.4	c.63+10189A>G		intron_variant, NMD_transcript_variant		2
ANK3	ENST00000510382.1	n.101+52910A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14076 AN: 152166 Hom.: 1182 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0865

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

GnomAD4 genome AF: 0.0925 AC: 14080 AN: 152284 Hom.: 1185 Cov.: 32 AF XY: 0.100 AC XY: 7476 AN XY: 74472

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.0798

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.0798

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.133 Hom.: 441

Bravo AF: 0.0960

Asia WGS AF: 0.251 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.4
Dann	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10994415; hg19: chr10-62322034;