chr5-272763-C-T

Position:

• chr5-272763-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_013232.4(PDCD6):​c.154C>T​(p.Leu52Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDCD6 NM_013232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0470

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a mutagenesis_site Strongly impaired interaction with SEC31A. Slightly reduced interaction with PDCD6IP. (size 0) in uniprot entity PDCD6_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD6	NM_013232.4	c.154C>T	p.Leu52Phe	missense_variant	2/6	ENST00000264933.9	NP_037364.1
PDCD6-AHRR	NR_165159.2	n.229C>T		non_coding_transcript_exon_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD6	ENST00000264933.9	c.154C>T	p.Leu52Phe	missense_variant	2/6	1	NM_013232.4	ENSP00000264933	P1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.91e-7 AC: 1 AN: 1448102 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 720266

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jan 19, 2022

The c.154C>T (p.L52F) alteration is located in exon 2 (coding exon 2) of the PDCD6 gene. This alteration results from a C to T substitution at nucleotide position 154, causing the leucine (L) at amino acid position 52 to be replaced by a phenylalanine (F). 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	0.99
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D;T;.;T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.029	N
LIST_S2	Pathogenic	0.98	D;D;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.52	D;D;D;D;D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	4.3	H;.;H;.;H;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.5	D;.;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;.;D;D;D;D
Sift4G	Pathogenic	0.0	D;T;D;D;D;D
Polyphen		0.97	D;.;.;.;.;.
Vest4		0.67
MutPred		0.69		Loss of stability (P = 0.1799);Loss of stability (P = 0.1799);Loss of stability (P = 0.1799);Loss of stability (P = 0.1799);Loss of stability (P = 0.1799);.;
MVP		0.96
MPC		3.0
ClinPred		0.94	D
GERP RS		0.11
Varity_R		0.54
gMVP		0.76

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: chr5-272878;