chr10-60084779-C-T

Variant names:

• chr10-60084779-C-T
• rs150367434
• NM_020987.5:c.3897G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_020987.5(ANK3):​c.3897G>A​(p.Thr1299Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,592,418 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (6 hom.)
• Consequence: ANK3 NM_020987.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.32
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-60084779-C-T is Benign according to our data. Variant chr10-60084779-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 434172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00109 (166/152226) while in subpopulation NFE AF = 0.00185 (126/68024). AF 95% confidence interval is 0.00159. There are 0 homozygotes in GnomAd4. There are 69 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR,Unknown,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020987.5. 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.3897G>A	p.Thr1299Thr	synonymous	Exon 32 of 44	NP_066267.2
	ANK3	NM_001204404.2		c.3900G>A	p.Thr1300Thr	synonymous	Exon 33 of 44	NP_001191333.1
	ANK3	NM_001320874.2		c.3897G>A	p.Thr1299Thr	synonymous	Exon 32 of 43	NP_001307803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK3	ENST00000280772.7	TSL:1 MANE Select	c.3897G>A	p.Thr1299Thr	synonymous	Exon 32 of 44	ENSP00000280772.1
	ANK3	ENST00000373827.6	TSL:1	c.3879G>A	p.Thr1293Thr	synonymous	Exon 33 of 44	ENSP00000362933.2
	ANK3	ENST00000355288.6	TSL:1	c.1299G>A	p.Thr433Thr	synonymous	Exon 10 of 21	ENSP00000347436.2

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 163 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00114 AC: 266 AN: 232346 AF XY: 0.00126

Gnomad AFR exome AF: 0.000633

Gnomad AMR exome AF: 0.000583

Gnomad ASJ exome AF: 0.000110

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000142

Gnomad NFE exome AF: 0.00191

Gnomad OTH exome AF: 0.00161

GnomAD4 exome AF: 0.00157 AC: 2264 AN: 1440192 Hom.: 6 Cov.: 31 AF XY: 0.00156 AC XY: 1113 AN XY: 714780

African (AFR) AF: 0.000520 AC: 17 AN: 32704

American (AMR) AF: 0.000697 AC: 28 AN: 40152

Ashkenazi Jewish (ASJ) AF: 0.0000394 AC: 1 AN: 25374

East Asian (EAS) AF: 0.00 AC: 0 AN: 39214

South Asian (SAS) AF: 0.000964 AC: 79 AN: 81942

European-Finnish (FIN) AF: 0.000283 AC: 15 AN: 52942

Middle Eastern (MID) AF: 0.00281 AC: 16 AN: 5684

European-Non Finnish (NFE) AF: 0.00181 AC: 1996 AN: 1102706

Other (OTH) AF: 0.00188 AC: 112 AN: 59474

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.000927 AC XY: 69 AN XY: 74414

African (AFR) AF: 0.000433 AC: 18 AN: 41546

American (AMR) AF: 0.000392 AC: 6 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4816

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68024

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00141 Hom.: 0

Bravo AF: 0.00106

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANK3: BP4, BP7

not specified Benign:1

Oct 31, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.1
DANN	Benign	0.71
PhyloP100		-1.3
Mutation Taster		=91/9	polymorphism

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: rs150367434; hg19: chr10-61844537; COSMIC: COSV55065796; COSMIC: COSV55065796;