10-60126134-G-T

Position:

• chr10-60126134-G-T

Variant summary

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

The NM_020987.5(ANK3):​c.2841+8137C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,944 control chromosomes in the GnomAD database, including 8,685 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 0.32 (8685 hom., cov: 31)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK3	NM_020987.5	c.2841+8137C>A		intron_variant		ENST00000280772.7	NP_066267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.2841+8137C>A		intron_variant		1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48679 AN: 151826 Hom.: 8681 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.321 AC: 48705 AN: 151944 Hom.: 8685 Cov.: 31 AF XY: 0.320 AC XY: 23733 AN XY: 74268

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.0694

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.318

Alfa AF: 0.358 Hom.: 1296

Bravo AF: 0.302

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.77
DANN	Benign	0.47

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: rs12761450; hg19: chr10-61885892;