10-60565907-G-T

Variant names:

• chr10-60565907-G-T
• rs10509132
• ENST00000373827.6:c.96+49279C>A

Variant summary

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

The NM_001204404.2(ANK3):​c.63+6558C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,914 control chromosomes in the GnomAD database, including 17,165 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 0.47 (17165 hom., cov: 32)
• Consequence: ANK3 NM_001204404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 6 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: Orphanet, Labcorp Genetics (formerly Invitae), 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=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204404.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_001204404.2		c.63+6558C>A		intron	N/A	NP_001191333.1	Q12955-4
	ANK3	NM_001204403.2		c.96+49279C>A		intron	N/A	NP_001191332.1	Q12955-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000373827.6	TSL:1	c.96+49279C>A		intron	N/A	ENSP00000362933.2	Q12955-5
	ANK3	ENST00000503366.6	TSL:2	c.63+6558C>A		intron	N/A	ENSP00000425236.1	Q12955-4
	ANK3	ENST00000510382.1	TSL:2	n.101+49279C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71358 AN: 151792 Hom.: 17168 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.470 AC: 71378 AN: 151914 Hom.: 17165 Cov.: 32 AF XY: 0.469 AC XY: 34791 AN XY: 74238

African (AFR) AF: 0.391 AC: 16191 AN: 41414

American (AMR) AF: 0.429 AC: 6551 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2314 AN: 5144

South Asian (SAS) AF: 0.496 AC: 2391 AN: 4816

European-Finnish (FIN) AF: 0.457 AC: 4818 AN: 10552

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.518 AC: 35217 AN: 67960

Other (OTH) AF: 0.504 AC: 1061 AN: 2104

Alfa AF: 0.480 Hom.: 9936

Bravo AF: 0.463

Asia WGS AF: 0.442 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.31
DANN	Benign	0.21
PhyloP100		-0.30
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: rs10509132; hg19: chr10-62325665;