chr10-60391257-C-T

Variant names:

• chr10-60391257-C-T
• rs3808943
• ENST00000373827.6:c.97-111618G>A

Variant summary

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

The ENST00000373827.6(ANK3):​c.97-111618G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,074 control chromosomes in the GnomAD database, including 1,129 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 0.10 (1129 hom., cov: 33)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204404.2	c.64-111618G>A		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001204403.2	c.97-111618G>A		intron_variant	Intron 2 of 43		NP_001191332.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK3	ENST00000373827.6	c.97-111618G>A		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000503366.6	c.64-111618G>A		intron_variant	Intron 1 of 43	2		ENSP00000425236.1
ANK3	ENST00000622427.4	n.64-111618G>A		intron_variant	Intron 1 of 32	2		ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15264 AN: 151954 Hom.: 1116 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.0894

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

GnomAD4 genome AF: 0.101 AC: 15308 AN: 152074 Hom.: 1129 Cov.: 33 AF XY: 0.108 AC XY: 8021 AN XY: 74338

African (AFR) AF: 0.0953 AC: 3955 AN: 41502

American (AMR) AF: 0.207 AC: 3160 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 132 AN: 3462

East Asian (EAS) AF: 0.261 AC: 1345 AN: 5150

South Asian (SAS) AF: 0.132 AC: 633 AN: 4812

European-Finnish (FIN) AF: 0.178 AC: 1880 AN: 10570

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0587 AC: 3989 AN: 67974

Other (OTH) AF: 0.0937 AC: 198 AN: 2114

Alfa AF: 0.109 Hom.: 275

Bravo AF: 0.104

Asia WGS AF: 0.213 AC: 737 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.68
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3808943; hg19: chr10-62151015;