Genetic Variant NM_013232.4:c.105C>G (chr5-272714-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_013232.4(PDCD6):c.105C>G(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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDCD6
NM_013232.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.358

Publications

0 publications found

Variant links:

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 links:

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-AHRR links:

ENSG00000286001 (HGNC:):

ENSG00000286001 links:

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

PDCD6-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-0.358 with no splicing effect.

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1430716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

708452

African (AFR)

AF:

0.00

AC:

AN:

29710

American (AMR)

AF:

0.00

AC:

AN:

41434

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25188

East Asian (EAS)

AF:

0.00

AC:

AN:

39220

South Asian (SAS)

AF:

0.00

AC:

AN:

84692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093660

Other (OTH)

AF:

0.00

AC:

AN:

58590

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.5

(source)

DANN

Benign

0.56

PhyloP100

-0.36

PromoterAI

0.051

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over