5-272714-C-A

Variant names:

• chr5-272714-C-A
• NM_013232.4:c.105C>A
• PDCD6 p.Val35Val

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013232.4(PDCD6):​c.105C>A​(p.Val35Val) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. V35V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: PDCD6 NM_013232.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 0 publications found

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]

ENSG00000286001 (HGNC:):

PDCD6-DT (HGNC:55580): (PDCD6 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD6	NM_013232.4	MANE Select	c.105C>A	p.Val35Val	synonymous	Exon 2 of 6	NP_037364.1	O75340-1
	PDCD6	NM_001267556.2		c.105C>A	p.Val35Val	synonymous	Exon 2 of 6	NP_001254485.1	O75340-2
	PDCD6	NM_001267557.2		c.105C>A	p.Val35Val	synonymous	Exon 2 of 4	NP_001254486.1	A0A087WZ38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD6	ENST00000264933.9	TSL:1 MANE Select	c.105C>A	p.Val35Val	synonymous	Exon 2 of 6	ENSP00000264933.4	O75340-1
	PDCD6	ENST00000507528.5	TSL:1	c.105C>A	p.Val35Val	synonymous	Exon 2 of 6	ENSP00000423815.1	O75340-2
	PDCD6	ENST00000509581.5	TSL:1	c.105C>A	p.Val35Val	synonymous	Exon 2 of 3	ENSP00000422691.1	Q86W51

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.0
DANN	Benign	0.67
PhyloP100		-0.36
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.24		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-272829;