chr5-272766-T-A

Position:

• chr5-272766-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_013232.4(PDCD6):​c.157T>A​(p.Ser53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 27)
• Consequence: PDCD6 NM_013232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

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

PDCD6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a mutagenesis_site Slightly reduced interaction with SEC31A. Does not affect interaction with PDCD6IP. (size 0) in uniprot entity PDCD6_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37851706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD6	NM_013232.4	c.157T>A	p.Ser53Thr	missense_variant	2/6	ENST00000264933.9	NP_037364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD6	ENST00000264933.9	c.157T>A	p.Ser53Thr	missense_variant	2/6	1	NM_013232.4	ENSP00000264933.4
ENSG00000286001	ENST00000651543.1	n.*1527T>A		non_coding_transcript_exon_variant	19/24			ENSP00000499215.1
PDCD6-AHRR	ENST00000675395.1	n.157T>A		non_coding_transcript_exon_variant	2/14			ENSP00000502570.1
ENSG00000286001	ENST00000651543.1	n.*1527T>A		3_prime_UTR_variant	19/24			ENSP00000499215.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 24, 2024

The c.157T>A (p.S53T) alteration is located in exon 2 (coding exon 2) of the PDCD6 gene. This alteration results from a T to A substitution at nucleotide position 157, causing the serine (S) at amino acid position 53 to be replaced by a threonine (T). 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	0.82
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Benign	0.83
DEOGEN2	Uncertain	0.47	T;T;.;T;.;.
Eigen	Benign	-0.047
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.38	T;T;T;T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	2.0	M;.;M;.;M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.4	N;.;D;D;N;N
REVEL	Benign	0.15
Sift	Benign	0.36	T;.;T;D;T;T
Sift4G	Benign	0.44	T;T;T;T;T;T
Polyphen		0.0010	B;.;.;.;.;.
Vest4		0.54
MutPred		0.49		Gain of catalytic residue at S53 (P = 0.121);Gain of catalytic residue at S53 (P = 0.121);Gain of catalytic residue at S53 (P = 0.121);Gain of catalytic residue at S53 (P = 0.121);Gain of catalytic residue at S53 (P = 0.121);.;
MVP		0.90
MPC		2.3
ClinPred		0.32	T
GERP RS		4.3
Varity_R		0.53
gMVP		0.54

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.

Other links and lift over

hg19: chr5-272881;