10-60267226-C-G

Variant names:

• chr10-60267226-C-G
• rs10761471
• NM_020987.5:c.513+2905G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020987.5(ANK3):​c.513+2905G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,860 control chromosomes in the GnomAD database, including 16,392 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 0.46 (16392 hom., cov: 32)
• Consequence: ANK3 NM_020987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_020987.5	c.513+2905G>C		intron_variant	Intron 5 of 43	ENST00000280772.7	NP_066267.2
ANK3	NM_001204404.2	c.462+2905G>C		intron_variant	Intron 5 of 43		NP_001191333.1
ANK3	NM_001320874.2	c.513+2905G>C		intron_variant	Intron 5 of 42		NP_001307803.1
ANK3	NM_001204403.2	c.495+2905G>C		intron_variant	Intron 6 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000280772.7	c.513+2905G>C		intron_variant	Intron 5 of 43	1	NM_020987.5	ENSP00000280772.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69572 AN: 151744 Hom.: 16389 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.458 AC: 69597 AN: 151860 Hom.: 16392 Cov.: 32 AF XY: 0.463 AC XY: 34341 AN XY: 74222

African (AFR) AF: 0.362 AC: 14968 AN: 41404

American (AMR) AF: 0.512 AC: 7817 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1525 AN: 3468

East Asian (EAS) AF: 0.643 AC: 3309 AN: 5148

South Asian (SAS) AF: 0.563 AC: 2711 AN: 4816

European-Finnish (FIN) AF: 0.497 AC: 5233 AN: 10520

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.479 AC: 32563 AN: 67918

Other (OTH) AF: 0.474 AC: 1002 AN: 2114

Alfa AF: 0.318 Hom.: 799

Bravo AF: 0.453

Asia WGS AF: 0.572 AC: 1981 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		0.29
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: rs10761471; hg19: chr10-62026984;