10-103403176-T-C

Position:

• chr10-103403176-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014976.2(PDCD11):​c.293T>C​(p.Leu98Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD11 NM_014976.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.293T>C	p.Leu98Pro	missense_variant	4/36	ENST00000369797.8	NP_055791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD11	ENST00000369797.8	c.293T>C	p.Leu98Pro	missense_variant	4/36	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.293T>C	p.Leu98Pro	missense_variant	4/36			ENSP00000498205.1
PDCD11	ENST00000493610.2	n.*360T>C		non_coding_transcript_exon_variant	5/6	5		ENSP00000474606.1
PDCD11	ENST00000493610.2	n.*360T>C		3_prime_UTR_variant	5/6	5		ENSP00000474606.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Mar 13, 2023

The c.293T>C (p.L98P) alteration is located in exon 4 (coding exon 3) of the PDCD11 gene. This alteration results from a T to C substitution at nucleotide position 293, causing the leucine (L) at amino acid position 98 to be replaced by a proline (P). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	.;T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Pathogenic	3.0	.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.9	.;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0030	.;D
Polyphen		1.0	.;D
Vest4		0.91
MutPred		0.86		Loss of stability (P = 0.0455);Loss of stability (P = 0.0455);
MVP		0.55
MPC		1.0
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.91

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: chr10-105162933;