Variant 6-105161593-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_022361.5(POPDC3):c.317G>A(p.Arg106Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,614,040 control chromosomes in the GnomAD database, including 953 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 (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.036 ( 116 hom., cov: 33)

Exomes 𝑓: 0.031 ( 837 hom. )

Consequence

POPDC3
NM_022361.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

POPDC3 (HGNC:17649): (popeye domain containing 3) This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in these tissues during development. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2008]

POPDC3 links:

BVES-AS1 (HGNC:21223): (BVES antisense RNA 1)

BVES-AS1 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=0.0022005439).

BP6

Variant 6-105161593-C-T is Benign according to our data. Variant chr6-105161593-C-T is described in ClinVar as [Benign]. Clinvar id is 1276858.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POPDC3	NM_022361.5 link	c.317G>A	p.Arg106Gln	missense_variant	Exon 2 of 4	ENST00000254765.4	NP_071756.2	Q9HBV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POPDC3	ENST00000254765.4 link	c.317G>A	p.Arg106Gln	missense_variant	Exon 2 of 4	1	NM_022361.5	ENSP00000254765.3		Q9HBV1

Frequencies

GnomAD3 genomes

AF:

0.0356

AC:

5412

AN:

152050

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0551

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0335

Gnomad OTH

AF:

0.0293

GnomAD3 exomes

AF:

0.0254

AC:

6378

AN:

251398

Hom.:

106

AF XY:

0.0251

AC XY:

3414

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0537

Gnomad AMR exome

AF:

0.0148

Gnomad ASJ exome

AF:

0.00794

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.0237

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0221

GnomAD4 exome

AF:

0.0312

AC:

45572

AN:

1461872

Hom.:

837

Cov.:

AF XY:

0.0307

AC XY:

22323

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0537

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.00735

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.0245

Gnomad4 NFE exome

AF:

0.0343

Gnomad4 OTH exome

AF:

0.0294

GnomAD4 genome

AF:

0.0356

AC:

5421

AN:

152168

Hom.:

116

Cov.:

AF XY:

0.0349

AC XY:

2597

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0553

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.0262

Gnomad4 NFE

AF:

0.0335

Gnomad4 OTH

AF:

0.0290

Alfa

AF:

0.0319

Hom.:

170

Bravo

AF:

0.0358

TwinsUK

AF:

0.0364

AC:

135

ALSPAC

AF:

0.0384

AC:

148

ESP6500AA

AF:

0.0524

AC:

231

ESP6500EA

AF:

0.0299

AC:

257

ExAC

AF:

0.0269

AC:

3271

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0331

EpiControl

AF:

0.0345

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

Eigen

Benign

-0.16

Eigen_PC

Benign

0.063

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.14

PrimateAI

Benign

0.28

PROVEAN

Benign

0.25

REVEL

Benign

0.051

Sift

Benign

0.27

Sift4G

Benign

0.32

Polyphen

0.0070

Vest4

0.11

MPC

0.22

ClinPred

0.0093

GERP RS

4.7

Varity_R

0.077

gMVP

0.34

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