Variant rs3748085 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001242809.2(ANKRD6):c.382A>G(p.Ile128Val) variant causes a missense change. The variant allele was found at a frequency of 0.834 in 1,587,258 control chromosomes in the GnomAD database, including 555,010 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.80 ( 49742 hom., cov: 33)

Exomes 𝑓: 0.84 ( 505268 hom. )

Consequence

ANKRD6
NM_001242809.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.00

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:

LOC124901359 (HGNC:):

LOC124901359 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.911872E-7).

BP6

Variant 6-89606070-A-G is Benign according to our data. Variant chr6-89606070-A-G is described in ClinVar as [Benign]. Clinvar id is 3060685.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD6	NM_001242809.2 linkuse as main transcript	c.382A>G	p.Ile128Val	missense_variant	5/16	ENST00000339746.9	NP_001229738.1
LOC124901359	XR_007059673.1 linkuse as main transcript	n.206-139T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD6	ENST00000339746.9 linkuse as main transcript	c.382A>G	p.Ile128Val	missense_variant	5/16	1	NM_001242809.2	ENSP00000345767	A1	Q9Y2G4-2

Frequencies

GnomAD3 genomes

AF:

0.804

AC:

122356

AN:

152096

Hom.:

49724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.691

Gnomad AMI

AF:

0.888

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.908

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.876

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.805

GnomAD3 exomes

AF:

0.830

AC:

178315

AN:

214964

Hom.:

74547

AF XY:

0.823

AC XY:

94914

AN XY:

115368

show subpopulations

Gnomad AFR exome

AF:

0.693

Gnomad AMR exome

AF:

0.892

Gnomad ASJ exome

AF:

0.829

Gnomad EAS exome

AF:

0.905

Gnomad SAS exome

AF:

0.683

Gnomad FIN exome

AF:

0.867

Gnomad NFE exome

AF:

0.846

Gnomad OTH exome

AF:

0.836

GnomAD4 exome

AF:

0.837

AC:

1201762

AN:

1435044

Hom.:

505268

Cov.:

AF XY:

0.833

AC XY:

592574

AN XY:

711126

show subpopulations

Gnomad4 AFR exome

AF:

0.688

Gnomad4 AMR exome

AF:

0.887

Gnomad4 ASJ exome

AF:

0.827

Gnomad4 EAS exome

AF:

0.930

Gnomad4 SAS exome

AF:

0.693

Gnomad4 FIN exome

AF:

0.867

Gnomad4 NFE exome

AF:

0.847

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.804

AC:

122421

AN:

152214

Hom.:

49742

Cov.:

AF XY:

0.806

AC XY:

59960

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.691

Gnomad4 AMR

AF:

0.866

Gnomad4 ASJ

AF:

0.832

Gnomad4 EAS

AF:

0.909

Gnomad4 SAS

AF:

0.700

Gnomad4 FIN

AF:

0.876

Gnomad4 NFE

AF:

0.845

Gnomad4 OTH

AF:

0.804

Alfa

AF:

0.836

Hom.:

133403

Bravo

AF:

0.801

TwinsUK

AF:

0.842

AC:

3122

ALSPAC

AF:

0.852

AC:

3285

ESP6500AA

AF:

0.717

AC:

2952

ESP6500EA

AF:

0.843

AC:

7075

ExAC

AF:

0.808

AC:

96698

Asia WGS

AF:

0.749

AC:

2602

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ANKRD6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

0.065

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.9

DANN

Benign

0.88

DEOGEN2

Benign

0.0041

.;T;.;T;T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.28

T;.;T;T;T;T

MetaRNN

Benign

5.9e-7

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;L;.;L;.

MutationTaster

Benign

1.0

P;P;P;P;P;P

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.44

N;N;N;N;N;N

REVEL

Benign

0.093

Sift

Benign

1.0

T;T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;B;.;.;B;.

Vest4

0.098

MPC

0.045

ClinPred

0.0028

GERP RS

4.1

Varity_R

0.021

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