Variant 1-1419158-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001145210.3(ANKRD65):c.1142C>T(p.Ala381Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,542,610 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0032 ( 28 hom. )

Consequence

ANKRD65
NM_001145210.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.44

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=0.002860576).

BP6

Variant 1-1419158-G-A is Benign according to our data. Variant chr1-1419158-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638008.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD65	NM_001145210.3 linkuse as main transcript	c.1142C>T	p.Ala381Val	missense_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.1142C>T	p.Ala381Val	missense_variant	4/4	5	NM_001145210.3	P1	E5RJM6-1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00409

AC:

606

AN:

148310

Hom.:

AF XY:

0.00448

AC XY:

356

AN XY:

79494

show subpopulations

Gnomad AFR exome

AF:

0.000997

Gnomad AMR exome

AF:

0.00465

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.000278

Gnomad SAS exome

AF:

0.00920

Gnomad FIN exome

AF:

0.0000660

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00638

GnomAD4 exome

AF:

0.00317

AC:

4413

AN:

1390256

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

2369

AN XY:

683828

show subpopulations

Gnomad4 AFR exome

AF:

0.000413

Gnomad4 AMR exome

AF:

0.00499

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.0000846

Gnomad4 SAS exome

AF:

0.00964

Gnomad4 FIN exome

AF:

0.000209

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.00437

GnomAD4 genome

AF:

0.00264

AC:

402

AN:

152354

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00890

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00314

Hom.:

Bravo

AF:

0.00273

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00234

AC:

ExAC

AF:

0.00579

AC:

131

Asia WGS

AF:

0.00231

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

Nov 01, 2022

ANKRD65: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.11

DANN

Benign

0.56

DEOGEN2

Benign

0.0023

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.27

T;.

MetaRNN

Benign

0.0029

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.21

N;.

REVEL

Benign

0.029

Sift

Benign

1.0

T;.

Sift4G

Benign

0.56

T;T

Polyphen

0.0010

B;B

Vest4

0.051

MVP

0.040

ClinPred

0.00059

GERP RS

-6.7

Varity_R

0.019

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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