NM_014976.2:c.735G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13306057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014976.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD11	NM_014976.2	MANE Select	c.735G>C	p.Lys245Asn	missense	Exon 7 of 36	NP_055791.1	Q14690
	PDCD11	NM_001411058.1		c.735G>C	p.Lys245Asn	missense	Exon 7 of 36	NP_001397987.1	A0A3B3IUD7
	PDCD11	NM_001437421.1		c.735G>C	p.Lys245Asn	missense	Exon 7 of 36	NP_001424350.1	A0A3B3IUD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD11	ENST00000369797.8	TSL:1 MANE Select	c.735G>C	p.Lys245Asn	missense	Exon 7 of 36	ENSP00000358812.3	Q14690
	PDCD11	ENST00000930114.1		c.735G>C	p.Lys245Asn	missense	Exon 7 of 37	ENSP00000600173.1
	PDCD11	ENST00000649849.1		c.735G>C	p.Lys245Asn	missense	Exon 7 of 36	ENSP00000498205.1	A0A3B3IUD7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		-0.11
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)
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
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr10-105166412;