Variant 1-1419337-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000427211.3(ANKRD65):c.422G>C(p.Cys141Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,550,404 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00079 ( 3 hom. )

Consequence

ANKRD65
ENST00000427211.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.742

Variant links:

Genes affected

ANKRD65 (HGNC:42950): (ankyrin repeat domain 65)

ANKRD65 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059562624).

BP6

Variant 1-1419337-C-G is Benign according to our data. Variant chr1-1419337-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638009.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD65	NM_001145210.3 linkuse as main transcript	c.963G>C	p.Leu321=	synonymous_variant	4/4	ENST00000537107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD65	ENST00000537107.6 linkuse as main transcript	c.963G>C	p.Leu321=	synonymous_variant	4/4	5	NM_001145210.3	P1	E5RJM6-1

Frequencies

GnomAD3 genomes

AF:

0.00316

AC:

481

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00878

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00131

AC:

201

AN:

153220

Hom.:

AF XY:

0.00109

AC XY:

AN XY:

81510

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.00284

Gnomad ASJ exome

AF:

0.000590

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000559

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.000790

AC:

1104

AN:

1398048

Hom.:

Cov.:

AF XY:

0.000763

AC XY:

526

AN XY:

689560

show subpopulations

Gnomad4 AFR exome

AF:

0.00965

Gnomad4 AMR exome

AF:

0.00305

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000497

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00318

AC:

484

AN:

152356

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

227

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00880

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.000872

Hom.:

Bravo

AF:

0.00373

ESP6500AA

AF:

0.0130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00108

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

ANKRD65: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Benign

0.44

DANN

Benign

0.62

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.15

.;T

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N;N

PROVEAN

Benign

0.97

N;N

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;D

Vest4

0.087

MutPred

0.32

Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);

MVP

0.067

ClinPred

0.016

GERP RS

0.074

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over