chr5-304180-C-A

Position:

• chr5-304180-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013232.4(PDCD6):​c.167C>A​(p.Thr56Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: PDCD6 NM_013232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.37

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41285744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD6	NM_013232.4	c.167C>A	p.Thr56Lys	missense_variant	3/6	ENST00000264933.9	NP_037364.1
PDCD6-AHRR	NR_165159.2	n.242C>A		non_coding_transcript_exon_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD6	ENST00000264933.9	c.167C>A	p.Thr56Lys	missense_variant	3/6	1	NM_013232.4	ENSP00000264933	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 29

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 12, 2024

The c.167C>A (p.T56K) alteration is located in exon 3 (coding exon 3) of the PDCD6 gene. This alteration results from a C to A substitution at nucleotide position 167, causing the threonine (T) at amino acid position 56 to be replaced by a lysine (K). 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	0.96
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.41	T
MutationTaster	Benign	1.0	D;D;D;D
Vest4		0.49
MVP		0.50
ClinPred		0.96	D
GERP RS		5.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr5-304295;