Variant 6-105161640-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_022361.5(POPDC3):c.270G>A(p.Met90Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,614,172 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

POPDC3
NM_022361.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.281

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=0.0048742294).

BP6

Variant 6-105161640-C-T is Benign according to our data. Variant chr6-105161640-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656803.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00188 (287/152292) while in subpopulation NFE AF= 0.0031 (211/68032). AF 95% confidence interval is 0.00276. There are 2 homozygotes in gnomad4. There are 144 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POPDC3	NM_022361.5 link	c.270G>A	p.Met90Ile	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.270G>A	p.Met90Ile	missense_variant	Exon 2 of 4	1	NM_022361.5	ENSP00000254765.3		Q9HBV1

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

288

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00491

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00151

AC:

379

AN:

251338

Hom.:

AF XY:

0.00139

AC XY:

189

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00467

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00169

AC:

2468

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1216

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00442

Gnomad4 NFE exome

AF:

0.00189

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00188

AC:

287

AN:

152292

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

144

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00491

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00207

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00170

AC:

207

EpiCase

AF:

0.00164

EpiControl

AF:

0.00202

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

Jul 01, 2024

POPDC3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0046

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.65

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.010

REVEL

Benign

0.087

Sift

Benign

0.73

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.19

MutPred

0.42

Gain of catalytic residue at M90 (P = 0.0792);

MVP

0.11

MPC

0.21

ClinPred

0.0067

GERP RS

2.9

Varity_R

0.044

gMVP

0.40

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