ENST00000373827.6:c.96+52910A>G

Variant names:

• chr10-60562276-T-C
• rs10994415
• ENST00000373827.6:c.96+52910A>G

Variant summary

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

The ENST00000373827.6(ANK3):​c.96+52910A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 152,284 control chromosomes in the GnomAD database, including 1,185 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 0.092 (1185 hom., cov: 32)
• Consequence: ANK3 ENST00000373827.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 20 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK3	NM_001204404.2	c.63+10189A>G		intron_variant	Intron 1 of 43		NP_001191333.1
ANK3	NM_001204403.2	c.96+52910A>G		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.96+52910A>G		intron_variant	Intron 2 of 43	1		ENSP00000362933.2
ANK3	ENST00000503366.6	c.63+10189A>G		intron_variant	Intron 1 of 43	2		ENSP00000425236.1
ANK3	ENST00000510382.1	n.101+52910A>G		intron_variant	Intron 2 of 2	2
ANK3	ENST00000622427.4	n.63+10189A>G		intron_variant	Intron 1 of 32	2		ENSP00000483244.1

Frequencies

GnomAD3 genomes AF: 0.0925 AC: 14076 AN: 152166 Hom.: 1182 Cov.: 32

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.0798

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.0865

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

GnomAD4 genome AF: 0.0925 AC: 14080 AN: 152284 Hom.: 1185 Cov.: 32 AF XY: 0.100 AC XY: 7476 AN XY: 74472

African (AFR) AF: 0.0185 AC: 769 AN: 41574

American (AMR) AF: 0.210 AC: 3206 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0798 AC: 277 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1677 AN: 5178

South Asian (SAS) AF: 0.174 AC: 840 AN: 4828

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0798 AC: 5425 AN: 68020

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

Alfa AF: 0.101 Hom.: 2159

Bravo AF: 0.0960

Asia WGS AF: 0.251 AC: 869 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.4
DANN	Benign	0.87
PhyloP100		0.17
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: rs10994415; hg19: chr10-62322034;