15-65133408-G-A

Position:

• chr15-65133408-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005707.2(PDCD7):​c.374C>T​(p.Ala125Val) variant causes a missense 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDCD7 NM_005707.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

Genes affected

PDCD7 (HGNC:8767): (programmed cell death 7) This gene encodes a 59 kDa protein that is associated with the U11 small nuclear ribonucleoprotein (snRNP), which is a component of the minor U12-type spliceosome responsible for catalyzing pre-mRNA splicing of U12-type introns. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.087343186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD7	NM_005707.2	c.374C>T	p.Ala125Val	missense_variant	1/5	ENST00000204549.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD7	ENST00000204549.9	c.374C>T	p.Ala125Val	missense_variant	1/5	1	NM_005707.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1034100 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 487780

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jul 25, 2023

The c.374C>T (p.A125V) alteration is located in exon 1 (coding exon 1) of the PDCD7 gene. This alteration results from a C to T substitution at nucleotide position 374, causing the alanine (A) at amino acid position 125 to be replaced by a valine (V). 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	Benign	0.078
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.025
Sift	Benign	0.18	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.17		Loss of glycosylation at P123 (P = 0.0789);
MVP		0.17
ClinPred		0.21	T
GERP RS		-0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.071
gMVP		0.24

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: chr15-65425746;