chr5-306694-A-C

Variant names:

• chr5-306694-A-C
• NM_013232.4:c.301A>C

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.35

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]

ENSG00000286001 (HGNC:):

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

ACMG classification

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	c.301A>C	p.Thr101Pro	missense_variant	Exon 4 of 6	ENST00000264933.9	NP_037364.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727172

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.: 32

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	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.39	T;.;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;T;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Uncertain	0.72	T
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	D
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.

Other links and lift over

hg19: chr5-306809;