Variant 6-89630727-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001242809.2(ANKRD6):c.1907C>T(p.Pro636Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,606 control chromosomes in the GnomAD database, including 14,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P636P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.099 ( 961 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13529 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.808

Variant links:

Genes affected

ANKRD6 (HGNC:17280): (ankyrin repeat domain 6) Predicted to be involved in negative regulation of canonical Wnt signaling pathway and positive regulation of JNK cascade. Predicted to act upstream of or within positive regulation of Wnt signaling pathway, planar cell polarity pathway. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ANKRD6 links:

LYRM2 (HGNC:25229): (LYR motif containing 2)

LYRM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011639893).

BP6

Variant 6-89630727-C-T is Benign according to our data. Variant chr6-89630727-C-T is described in ClinVar as [Benign]. Clinvar id is 3060598.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD6	NM_001242809.2 linkuse as main transcript	c.1907C>T	p.Pro636Leu	missense_variant	16/16	ENST00000339746.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD6	ENST00000339746.9 linkuse as main transcript	c.1907C>T	p.Pro636Leu	missense_variant	16/16	1	NM_001242809.2	A1	Q9Y2G4-2

Frequencies

GnomAD3 genomes

AF:

0.0988

AC:

15042

AN:

152172

Hom.:

963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0245

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0876

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0513

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.124

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.117

AC:

29158

AN:

248226

Hom.:

1951

AF XY:

0.124

AC XY:

16771

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.0196

Gnomad AMR exome

AF:

0.0660

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.0563

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.127

GnomAD4 exome

AF:

0.132

AC:

193138

AN:

1461316

Hom.:

13529

Cov.:

AF XY:

0.135

AC XY:

97779

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.0206

Gnomad4 AMR exome

AF:

0.0691

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.0454

Gnomad4 SAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.0987

AC:

15030

AN:

152290

Hom.:

961

Cov.:

AF XY:

0.0980

AC XY:

7293

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0244

Gnomad4 AMR

AF:

0.0875

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.0509

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.124

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.129

Hom.:

2221

Bravo

AF:

0.0928

TwinsUK

AF:

0.147

AC:

546

ALSPAC

AF:

0.141

AC:

542

ESP6500AA

AF:

0.0242

AC:

102

ESP6500EA

AF:

0.139

AC:

1177

ExAC

AF:

0.120

AC:

14492

Asia WGS

AF:

0.103

AC:

359

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.151

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ANKRD6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

6.8

DANN

Benign

0.94

DEOGEN2

Benign

0.014

.;T;.;T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.71

T;.;T;T;T

MetaRNN

Benign

0.0012

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;.;L;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.043

Sift

Uncertain

0.029

D;D;D;D;D

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.55

P;P;.;P;.

Vest4

0.062

MPC

0.052

ClinPred

0.028

GERP RS

1.6

Varity_R

0.053

gMVP

0.16

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