Variant chr6-46752082-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_001162435.3(ANKRD66):c.134G>A(p.Arg45Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000246 in 1,509,742 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 5 hom. )

Consequence

ANKRD66
NM_001162435.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

ANKRD66 (HGNC:44669): (ankyrin repeat domain 66)

ANKRD66 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=0.0074315965).

BP6

Variant 6-46752082-G-A is Benign according to our data. Variant chr6-46752082-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2343638.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD66	NM_001162435.3 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	3/5	ENST00000565422.3
ANKRD66	XM_017010148.2 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD66	ENST00000565422.3 linkuse as main transcript	c.134G>A	p.Arg45Gln	missense_variant	3/5	2	NM_001162435.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00203

AC:

221

AN:

108950

Hom.:

AF XY:

0.00164

AC XY:

AN XY:

57970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000460

Gnomad OTH exome

AF:

0.00170

GnomAD4 exome

AF:

0.000231

AC:

313

AN:

1357482

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

132

AN XY:

668602

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000617

Gnomad4 SAS exome

AF:

0.0000413

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000941

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

AF:

0.000387

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000973

Hom.:

Bravo

AF:

0.000948

ExAC

AF:

0.000179

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.027

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.0074

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.84

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.0

Sift

Benign

0.092

Sift4G

Uncertain

0.033

Vest4

0.40

MVP

0.64

GERP RS

5.6

Varity_R

0.24

gMVP

0.29

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