10-103417888-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014976.2(PDCD11):​c.1867G>T​(p.Ala623Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,614,016 control chromosomes in the GnomAD database, including 3,647 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.047 (221 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3426 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022095144).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD11	NM_014976.2	c.1867G>T	p.Ala623Ser	missense_variant	Exon 14 of 36	ENST00000369797.8	NP_055791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD11	ENST00000369797.8	c.1867G>T	p.Ala623Ser	missense_variant	Exon 14 of 36	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1	c.1867G>T	p.Ala623Ser	missense_variant	Exon 14 of 36			ENSP00000498205.1
ENSG00000301927	ENST00000782928.1	n.251-3C>A		splice_region_variant, intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0466 AC: 7092 AN: 152168 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0540

GnomAD2 exomes AF: 0.0502 AC: 12617 AN: 251430 AF XY: 0.0508

Gnomad AFR exome AF: 0.0151

Gnomad AMR exome AF: 0.0403

Gnomad ASJ exome AF: 0.0927

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.0716

Gnomad OTH exome AF: 0.0662

GnomAD4 exome AF: 0.0648 AC: 94741 AN: 1461730 Hom.: 3426 Cov.: 32 AF XY: 0.0639 AC XY: 46485 AN XY: 727158

African (AFR) AF: 0.0116 AC: 387 AN: 33480

American (AMR) AF: 0.0408 AC: 1824 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0921 AC: 2407 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0297 AC: 2558 AN: 86256

European-Finnish (FIN) AF: 0.0294 AC: 1573 AN: 53420

Middle Eastern (MID) AF: 0.103 AC: 592 AN: 5768

European-Non Finnish (NFE) AF: 0.0735 AC: 81694 AN: 1111866

Other (OTH) AF: 0.0613 AC: 3703 AN: 60394

GnomAD4 genome AF: 0.0466 AC: 7091 AN: 152286 Hom.: 221 Cov.: 32 AF XY: 0.0443 AC XY: 3300 AN XY: 74470

African (AFR) AF: 0.0144 AC: 600 AN: 41576

American (AMR) AF: 0.0500 AC: 765 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 324 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4818

European-Finnish (FIN) AF: 0.0236 AC: 250 AN: 10612

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0690 AC: 4690 AN: 68008

Other (OTH) AF: 0.0534 AC: 113 AN: 2116

Alfa AF: 0.0641 Hom.: 1176

Bravo AF: 0.0478

TwinsUK AF: 0.0739 AC: 274

ALSPAC AF: 0.0701 AC: 270

ESP6500AA AF: 0.0179 AC: 79

ESP6500EA AF: 0.0695 AC: 598

ExAC AF: 0.0496 AC: 6027

Asia WGS AF: 0.0150 AC: 56 AN: 3478

EpiCase AF: 0.0741

EpiControl AF: 0.0768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.83
DEOGEN2	Benign	0.0059	.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.43	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	.;N
PhyloP100		0.12
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.31	.;N
REVEL	Benign	0.035
Sift	Benign	0.76	.;T
Sift4G	Benign	0.64	.;T
Polyphen		0.0040	.;B
Vest4		0.065
MPC		0.19
ClinPred		0.0020	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.21
Mutation Taster		=98/2	polymorphism (auto)

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; COSMIC: COSV63933877;