rs139423894

Variant names:

• chr10-103406667-C-T
• rs139423894
• NM_014976.2:c.747C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_014976.2(PDCD11):​c.747C>T​(p.Asn249Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000924 in 1,614,064 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (11 hom.)
• Consequence: PDCD11 NM_014976.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.54
• Publications: 3 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-103406667-C-T is Benign according to our data. Variant chr10-103406667-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2640803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.54 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000913 (1335/1461852) while in subpopulation MID AF = 0.0217 (125/5768). AF 95% confidence interval is 0.0186. There are 11 homozygotes in GnomAdExome4. There are 690 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 156 AD gene.

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.747C>T	p.Asn249Asn	synonymous	Exon 7 of 36	NP_055791.1	Q14690
	PDCD11	NM_001411058.1		c.747C>T	p.Asn249Asn	synonymous	Exon 7 of 36	NP_001397987.1	A0A3B3IUD7
	PDCD11	NM_001437421.1		c.747C>T	p.Asn249Asn	synonymous	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.747C>T	p.Asn249Asn	synonymous	Exon 7 of 36	ENSP00000358812.3	Q14690
	PDCD11	ENST00000930114.1		c.747C>T	p.Asn249Asn	synonymous	Exon 7 of 37	ENSP00000600173.1
	PDCD11	ENST00000649849.1		c.747C>T	p.Asn249Asn	synonymous	Exon 7 of 36	ENSP00000498205.1	A0A3B3IUD7

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152094 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00116 AC: 292 AN: 251490 AF XY: 0.00108

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000809

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000861

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.000913 AC: 1335 AN: 1461852 Hom.: 11 Cov.: 31 AF XY: 0.000949 AC XY: 690 AN XY: 727230

African (AFR) AF: 0.00131 AC: 44 AN: 33480

American (AMR) AF: 0.00110 AC: 49 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 315 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.0217 AC: 125 AN: 5768

European-Non Finnish (NFE) AF: 0.000576 AC: 641 AN: 1111976

Other (OTH) AF: 0.00215 AC: 130 AN: 60396

GnomAD4 genome AF: 0.00102 AC: 156 AN: 152212 Hom.: 2 Cov.: 32 AF XY: 0.00117 AC XY: 87 AN XY: 74400

African (AFR) AF: 0.000289 AC: 12 AN: 41534

American (AMR) AF: 0.00151 AC: 23 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.000676 AC: 46 AN: 68024

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00178 Hom.: 0

Bravo AF: 0.000945

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.21
DANN	Benign	0.45
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs139423894; hg19: chr10-105166424; COSMIC: COSV100874273; COSMIC: COSV100874273;