dbSNP rs761977523: PDCD6:p.Thr101Pro (chr5-306694-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013232.4(PDCD6):c.301A>C(p.Thr101Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PDCD6
NM_013232.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.35

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:

ENSG00000286001 (HGNC:):

ENSG00000286001 links:

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDCD6-AHRR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD6	NM_013232.4 link	c.301A>C	p.Thr101Pro	missense_variant	Exon 4 of 6	ENST00000264933.9	NP_037364.1	O75340-1Q53FC3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDCD6	ENST00000264933.9 link	c.301A>C	p.Thr101Pro	missense_variant	Exon 4 of 6	1	NM_013232.4	ENSP00000264933.4	O75340-1
ENSG00000286001	ENST00000651543.1 link	n.*1671A>C		non_coding_transcript_exon_variant	Exon 21 of 24			ENSP00000499215.1	A0A494C1T6
ENSG00000286001	ENST00000651543.1 link	n.*1671A>C		3_prime_UTR_variant	Exon 21 of 24			ENSP00000499215.1	A0A494C1T6
PDCD6-AHRR	ENST00000675395.1 link	n.208+2473A>C		intron_variant	Intron 3 of 13			ENSP00000502570.1	A0A6Q8PH81

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727172

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.39

T;.;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;T;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Uncertain

2.7

M;.;M

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.6

D;.;D

REVEL

Uncertain

0.45

Sift

Benign

0.081

T;.;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.010

B;.;.

Vest4

0.67

MutPred

0.52

Loss of phosphorylation at T101 (P = 0.0502);.;Loss of phosphorylation at T101 (P = 0.0502);

MVP

0.93

MPC

1.1

ClinPred

0.60

GERP RS

5.5

Varity_R

0.77

gMVP

0.89

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over