rs150367434

chr10-60084779-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_020987.5(ANK3):c.3897G>A(p.Thr1299=) 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:3
• Conservation: PhyloP100: -1.32

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]

ACMG classification

Verdict is Benign. Variant got -13 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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.3897G>A	p.Thr1299=	synonymous_variant	32/44	ENST00000280772.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.3897G>A	p.Thr1299=	synonymous_variant	32/44	1	NM_020987.5

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

GnomAD3 exomes AF: 0.00114 AC: 266 AN: 232346 Hom.: 0 AF XY: 0.00126 AC XY: 159 AN XY: 125702

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 SAS exome AF: 0.000731

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

Gnomad4 AFR exome AF: 0.000520

Gnomad4 AMR exome AF: 0.000697

Gnomad4 ASJ exome AF: 0.0000394

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000964

Gnomad4 FIN exome AF: 0.000283

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00188

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

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.000950

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	ANK3: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 31, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	4.1
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

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