rs142415903

chr10-60181410-G-Achr10-60181410-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_020987.5(ANK3):c.2103C>T(p.Leu701=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,614,160 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (15 hom.)
• Consequence: ANK3 NM_020987.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.07

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 10-60181410-G-A is Benign according to our data. Variant chr10-60181410-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.07 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK3	NM_020987.5	c.2103C>T	p.Leu701=	synonymous_variant	18/44	ENST00000280772.7
ANK3	NM_001204404.2	c.2052C>T	p.Leu684=	synonymous_variant	18/44
ANK3	NM_001320874.2	c.2103C>T	p.Leu701=	synonymous_variant	18/43
ANK3	NM_001204403.2	c.2085C>T	p.Leu695=	synonymous_variant	19/44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK3	ENST00000280772.7	c.2103C>T	p.Leu701=	synonymous_variant	18/44	1	NM_020987.5

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 450 AN: 152190 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00547

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00298 AC: 748 AN: 251386 Hom.: 4 AF XY: 0.00283 AC XY: 384 AN XY: 135864

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.00556

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00550

Gnomad NFE exome AF: 0.00448

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00352 AC: 5149 AN: 1461852 Hom.: 15 Cov.: 31 AF XY: 0.00351 AC XY: 2551 AN XY: 727234

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000961

Gnomad4 ASJ exome AF: 0.00566

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00453

Gnomad4 NFE exome AF: 0.00404

Gnomad4 OTH exome AF: 0.00311

GnomAD4 genome AF: 0.00295 AC: 450 AN: 152308 Hom.: 2 Cov.: 32 AF XY: 0.00279 AC XY: 208 AN XY: 74478

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00547

Gnomad4 NFE AF: 0.00426

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00263

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00496

EpiControl AF: 0.00480

ClinVar

Significance: Benign/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, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	2.8
Dann	Benign	0.79

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: rs142415903; hg19: chr10-61941168;