NM_014976.2:c.1867G>A

Variant names:

• chr10-103417888-G-A
• rs11598673
• NM_014976.2:c.1867G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014976.2(PDCD11):​c.1867G>A​(p.Ala623Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD11 NM_014976.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124
• Publications: 22 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]

ENSG00000301927 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061559677).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD11	NM_014976.2	MANE Select	c.1867G>A	p.Ala623Thr	missense	Exon 14 of 36	NP_055791.1
	PDCD11	NM_001411058.1		c.1867G>A	p.Ala623Thr	missense	Exon 14 of 36	NP_001397987.1
	PDCD11	NM_001437421.1		c.1867G>A	p.Ala623Thr	missense	Exon 14 of 36	NP_001424350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD11	ENST00000369797.8	TSL:1 MANE Select	c.1867G>A	p.Ala623Thr	missense	Exon 14 of 36	ENSP00000358812.3
	PDCD11	ENST00000649849.1		c.1867G>A	p.Ala623Thr	missense	Exon 14 of 36	ENSP00000498205.1
	ENSG00000301927	ENST00000782928.1		n.251-3C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.3
DANN	Benign	0.90
DEOGEN2	Benign	0.0072	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.12
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.037
Sift	Benign	0.59	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.27		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.24
MPC		0.20
ClinPred		0.038	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.017
gMVP		0.20
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs11598673; hg19: chr10-105177645;