10-60317078-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.115-37439C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,754 control chromosomes in the GnomAD database, including 26,062 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 0.58 (26062 hom., cov: 31)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.115-37439C>A		intron_variant		ENST00000280772.7
ANK3	NM_001204403.2	c.97-37439C>A		intron_variant
ANK3	NM_001204404.2	c.64-37439C>A		intron_variant
ANK3	NM_001320874.2	c.115-37439C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.115-37439C>A		intron_variant		1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87857 AN: 151636 Hom.: 26046 Cov.: 31

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.579 AC: 87919 AN: 151754 Hom.: 26062 Cov.: 31 AF XY: 0.583 AC XY: 43242 AN XY: 74162

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.619

Alfa AF: 0.586 Hom.: 4479

Bravo AF: 0.575

Asia WGS AF: 0.708 AC: 2462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.9
Dann	Benign	0.82

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: rs10761481; hg19: chr10-62076836;