10-60081386-A-G

Variant names:

• chr10-60081386-A-G
• rs7098848
• NM_020987.5:c.4350+764T>C

Variant summary

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

The ENST00000280772.7(ANK3):​c.4350+764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 287,250 control chromosomes in the GnomAD database, including 1,971 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 0.12 (1314 hom., cov: 32)
  • Exomes 𝑓: 0.082 (657 hom.)
• Consequence: ANK3 ENST00000280772.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• 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)

ENSG00000232682 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000280772.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	NM_020987.5	MANE Select	c.4350+764T>C		intron	N/A	NP_066267.2
	ANK3	NM_001204404.2		c.4327-768T>C		intron	N/A	NP_001191333.1
	ANK3	NM_001320874.2		c.4324-768T>C		intron	N/A	NP_001307803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.4350+764T>C		intron	N/A	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.4306-768T>C		intron	N/A	ENSP00000362933.2
	ANK3	ENST00000355288.6	TSL:1	c.1726-768T>C		intron	N/A	ENSP00000347436.2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18353 AN: 152068 Hom.: 1313 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0883

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0768

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.0818 AC: 11043 AN: 135066 Hom.: 657 AF XY: 0.0764 AC XY: 5921 AN XY: 77526

African (AFR) AF: 0.179 AC: 611 AN: 3416

American (AMR) AF: 0.0670 AC: 476 AN: 7100

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 222 AN: 3172

East Asian (EAS) AF: 0.000186 AC: 1 AN: 5376

South Asian (SAS) AF: 0.0186 AC: 487 AN: 26124

European-Finnish (FIN) AF: 0.0889 AC: 483 AN: 5432

Middle Eastern (MID) AF: 0.0944 AC: 196 AN: 2076

European-Non Finnish (NFE) AF: 0.106 AC: 8027 AN: 75886

Other (OTH) AF: 0.0833 AC: 540 AN: 6484

GnomAD4 genome AF: 0.121 AC: 18369 AN: 152184 Hom.: 1314 Cov.: 32 AF XY: 0.115 AC XY: 8567 AN XY: 74400

African (AFR) AF: 0.193 AC: 8018 AN: 41514

American (AMR) AF: 0.0883 AC: 1350 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4820

European-Finnish (FIN) AF: 0.0768 AC: 814 AN: 10594

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7582 AN: 68008

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.115 Hom.: 212

Bravo AF: 0.125

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.68
DANN	Benign	0.73
PhyloP100		-1.7
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: rs7098848; hg19: chr10-61841144;