Variant chr5-272758-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013232.4(PDCD6):c.149A>G(p.Gln50Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000029 in 1,448,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDCD6
NM_013232.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

PDCD6 (HGNC:8765): (programmed cell death 6) This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]

PDCD6 links:

PDCD6-AHRR (HGNC:):

PDCD6-AHRR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29332212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD6	NM_013232.4 linkuse as main transcript	c.149A>G	p.Gln50Arg	missense_variant	2/6	ENST00000264933.9	NP_037364.1
PDCD6-AHRR	NR_165159.2 linkuse as main transcript	n.224A>G		non_coding_transcript_exon_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD6	ENST00000264933.9 linkuse as main transcript	c.149A>G	p.Gln50Arg	missense_variant	2/6	1	NM_013232.4	ENSP00000264933	P1	O75340-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

139198

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238168

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

130168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000290

AC:

AN:

1448422

Hom.:

Cov.:

AF XY:

0.0000236

AC XY:

AN XY:

720308

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000362

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

139198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68020

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000829

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.149A>G (p.Q50R) alteration is located in exon 2 (coding exon 2) of the PDCD6 gene. This alteration results from a A to G substitution at nucleotide position 149, causing the glutamine (Q) at amino acid position 50 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.17

T;T;.;T;.;.

Eigen

Benign

-0.084

Eigen_PC

Benign

-0.016

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.91

D;D;D;D;D;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.29

T;T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.92

L;.;L;.;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

N;.;N;D;N;N

REVEL

Benign

0.16

Sift

Benign

0.11

T;.;T;D;T;T

Sift4G

Benign

0.26

T;T;T;D;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.63

MVP

0.93

MPC

2.0

ClinPred

0.21

GERP RS

4.3

Varity_R

0.28

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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