10-60081386-A-G

Position:

• chr10-60081386-A-G

Variant summary

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

The NM_020987.5(ANK3):​c.4350+764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 287,250 control chromosomes in the GnomAD database, including 1,971 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 0.12 (1314 hom., cov: 32)
  • Exomes 𝑓: 0.082 (657 hom.)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.4350+764T>C		intron_variant		ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.4350+764T>C		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18353 AN: 152068 Hom.: 1313 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0818 AC: 11043 AN: 135066 Hom.: 657 AF XY: 0.0764 AC XY: 5921 AN XY: 77526

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0670

Gnomad4 ASJ exome AF: 0.0700

Gnomad4 EAS exome AF: 0.000186

Gnomad4 SAS exome AF: 0.0186

Gnomad4 FIN exome AF: 0.0889

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.121 AC: 18369 AN: 152184 Hom.: 1314 Cov.: 32 AF XY: 0.115 AC XY: 8567 AN XY: 74400

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.0583

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0768

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.107

Alfa AF: 0.115 Hom.: 212

Bravo AF: 0.125

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7098848; hg19: chr10-61841144;