3-167695690-G-C

Position:

• chr3-167695690-G-C

Variant summary

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

The NM_007217.4(PDCD10):​c.301C>G​(p.Gln101Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,190 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q101R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PDCD10 NM_007217.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.86

Genes affected

PDCD10 (HGNC:8761): (programmed cell death 10) This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25, and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations, which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

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/exons	MANE	UniProt
PDCD10	NM_007217.4	c.301C>G	p.Gln101Glu	missense_variant	6/9	ENST00000392750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD10	ENST00000392750.7	c.301C>G	p.Gln101Glu	missense_variant	6/9	1	NM_007217.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461190 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726992

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: 0.0000187

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T;T;T;T;T;T;T;.;.;.;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M;M;.;M;M;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.077	T;T;T;T;T;T;D;T;T;T;D
Sift4G	Benign	0.94	T;T;T;T;T;T;.;T;T;.;T
Polyphen		0.13	B;B;B;.;B;B;.;.;.;.;.
Vest4		0.74
MutPred		0.53		Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);.;Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);Loss of glycosylation at P98 (P = 0.0328);
MVP		0.75
MPC		0.73
ClinPred		0.89	D
GERP RS		4.5
Varity_R		0.67
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs1303470125; hg19: chr3-167413478;