10-103398520-T-G

Position:

• chr10-103398520-T-G

Variant summary

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

The NM_014976.2(PDCD11):​c.94T>G​(p.Leu32Val) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDCD11 NM_014976.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

Genes affected

PDCD11 (HGNC:13408): (programmed cell death 11) PDCD11 is a NF-kappa-B (NFKB1; 164011)-binding protein that colocalizes with U3 RNA (MIM 180710) in the nucleolus and is required for rRNA maturation and generation of 18S rRNA (Sweet et al., 2003 [PubMed 14624448]; Sweet et al., 2008 [PubMed 17654514]).[supplied by OMIM, Oct 2008]

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=0.23542607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.94T>G	p.Leu32Val	missense_variant	2/36	ENST00000369797.8	NP_055791.1
PDCD11	NM_001411058.1	c.94T>G	p.Leu32Val	missense_variant	2/36		NP_001397987.1
PDCD11	XM_005269647.4	c.94T>G	p.Leu32Val	missense_variant	2/36		XP_005269704.1
PDCD11	XM_011539539.3	c.94T>G	p.Leu32Val	missense_variant	2/36		XP_011537841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD11	ENST00000369797.8	c.94T>G	p.Leu32Val	missense_variant	2/36	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.94T>G	p.Leu32Val	missense_variant	2/36			ENSP00000498205.1
PDCD11	ENST00000493610.2	n.94T>G		non_coding_transcript_exon_variant	2/6	5		ENSP00000474606.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Nov 08, 2024

The c.94T>G (p.L32V) alteration is located in exon 2 (coding exon 1) of the PDCD11 gene. This alteration results from a T to G substitution at nucleotide position 94, causing the leucine (L) at amino acid position 32 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	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.2	.;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.6	.;N
REVEL	Benign	0.12
Sift	Uncertain	0.022	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	.;D
Vest4		0.42
MutPred		0.22		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.32
MPC		0.78
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.52

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: rs2093449017; hg19: chr10-105158277;