rs560438483

Variant names:

• chr10-103398431-C-G
• rs560438483
• NM_014976.2:c.5C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-103398431-C-G
• chr10-103398431-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_014976.2(PDCD11):​c.5C>G​(p.Ala2Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PDCD11 NM_014976.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

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 3 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity RRP5_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3081723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 36	ENST00000369797.8	NP_055791.1
PDCD11	NM_001411058.1	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 36		NP_001397987.1
PDCD11	XM_005269647.4	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 36		XP_005269704.1
PDCD11	XM_011539539.3	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 36		XP_011537841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD11	ENST00000369797.8	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 36	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 36			ENSP00000498205.1
PDCD11	ENST00000493610.2	n.5C>G		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000474606.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460010 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	.;N
REVEL	Benign	0.087
Sift	Uncertain	0.013	.;D
Sift4G	Benign	0.079	.;T
Polyphen		0.82	.;P
Vest4		0.35
MutPred		0.14		Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);
MVP		0.42
MPC		0.24
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.35

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: rs560438483; hg19: chr10-105158188;