10-103406655-G-C

Variant names:

• chr10-103406655-G-C
• NM_014976.2:c.735G>C

Variant summary

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

The NM_014976.2(PDCD11):​c.735G>C​(p.Lys245Asn) 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. 15/21 in silico tools predict a benign 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: -0.111

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=0.13306057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.735G>C	p.Lys245Asn	missense_variant	Exon 7 of 36	ENST00000369797.8	NP_055791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD11	ENST00000369797.8	c.735G>C	p.Lys245Asn	missense_variant	Exon 7 of 36	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.735G>C	p.Lys245Asn	missense_variant	Exon 7 of 36			ENSP00000498205.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.735G>C (p.K245N) alteration is located in exon 7 (coding exon 6) of the PDCD11 gene. This alteration results from a G to C substitution at nucleotide position 735, causing the lysine (K) at amino acid position 245 to be replaced by an asparagine (N). 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	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	.;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.025
Sift	Uncertain	0.0070	.;D
Sift4G	Uncertain	0.013	.;D
Polyphen		0.0060	.;B
Vest4		0.21
MutPred		0.42		Loss of ubiquitination at K245 (P = 0.0167);Loss of ubiquitination at K245 (P = 0.0167);
MVP		0.49
MPC		0.31
ClinPred		0.82	D
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-105166412;