rs1049862

Positions:

• chr10-60029514-G-A
• chr10-60029514-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020987.5(ANK3):​c.*332C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.361 in 152,434 control chromosomes in the GnomAD database, including 12,436 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 0.36 (12404 hom., cov: 31)
  • Exomes 𝑓: 0.36 (32 hom.)
• Consequence: ANK3 NM_020987.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.08

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.*332C>T		3_prime_UTR_variant	44/44	ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772	c.*332C>T		3_prime_UTR_variant	44/44	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54849 AN: 151884 Hom.: 12399 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.361 AC: 156 AN: 432 Hom.: 32 Cov.: 0 AF XY: 0.377 AC XY: 98 AN XY: 260

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.361 AC: 54862 AN: 152002 Hom.: 12404 Cov.: 31 AF XY: 0.356 AC XY: 26428 AN XY: 74274

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.418

Alfa AF: 0.367 Hom.: 2615

Bravo AF: 0.347

Asia WGS AF: 0.354 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.80

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: rs1049862; hg19: chr10-61789272;