rs10509138

chr10-60678152-A-Cchr10-60678152-A-T

Variant summary

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

The ENST00000373827.6(ANK3):c.57+55111T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,266 control chromosomes in the GnomAD database, including 1,449 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 0.11 (1449 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

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 = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_001204403.2	c.57+55111T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000373827.6	c.57+55111T>G		intron_variant		1
ANK3	ENST00000510382.1	n.62+55111T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17195 AN: 152148 Hom.: 1441 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.113 AC: 17213 AN: 152266 Hom.: 1449 Cov.: 32 AF XY: 0.118 AC XY: 8821 AN XY: 74440

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0552 Hom.: 53

Bravo AF: 0.117

Asia WGS AF: 0.255 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.68
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10509138; hg19: chr10-62437910;