10-60317078-G-T

Variant names:

• chr10-60317078-G-T
• rs10761481
• NM_020987.5:c.115-37439C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ANK3 Gene-Disease associations (from GenCC):

• intellectual disability-hypotonia-spasticity-sleep disorder syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• intellectual disability

  Inheritance: AR, AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.115-37439C>A		intron_variant	Intron 1 of 43	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.64-37439C>A		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001320874.2	c.115-37439C>A		intron_variant	Intron 1 of 42		NP_001307803.1
ANK3	NM_001204403.2	c.97-37439C>A		intron_variant	Intron 2 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.115-37439C>A		intron_variant	Intron 1 of 43	1	NM_020987.5	ENSP00000280772.1

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

African (AFR) AF: 0.461 AC: 19029 AN: 41312

American (AMR) AF: 0.641 AC: 9796 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2377 AN: 3466

East Asian (EAS) AF: 0.710 AC: 3636 AN: 5122

South Asian (SAS) AF: 0.766 AC: 3679 AN: 4804

European-Finnish (FIN) AF: 0.566 AC: 5979 AN: 10558

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41374 AN: 67914

Other (OTH) AF: 0.619 AC: 1303 AN: 2106

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
PhyloP100		-0.060
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10761481; hg19: chr10-62076836;