NM_001077663.3:c.2014G>A

Variant names:

• chr7-43877449-C-T
• rs201208471
• NM_001077663.3:c.2014G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001077663.3(URGCP):​c.2014G>A​(p.Val672Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,613,584 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000065 (1 hom.)
• Consequence: URGCP NM_001077663.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137
• Publications: 2 publications found

Genes affected

URGCP (HGNC:30890): (upregulator of cell proliferation) URG4 is upregulated in the presence of hepatitis B virus (HBV)-encoded X antigen (HBxAg) and may contribute to the development of hepatocellular carcinoma by promoting hepatocellular growth and survival (Tufan et al., 2002 [PubMed 12082552]).[supplied by OMIM, Mar 2008]

URGCP-MRPS24 (HGNC:49188): (URGCP-MRPS24 readthrough) This locus represents naturally occurring read-through transcription between the neighboring URGCP (upregulator of cell proliferation) and MRPS24 (mitochondrial ribosomal protein S24) genes on chromosome 7. The read-through transcript is predicted to encode a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to a frameshift relative to the downstream gene. [provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014028579).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077663.3. 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
	URGCP	NM_001077663.3	MANE Select	c.2014G>A	p.Val672Ile	missense	Exon 6 of 6	NP_001071131.1	Q8TCY9-1
	URGCP	NM_017920.5		c.1987G>A	p.Val663Ile	missense	Exon 5 of 5	NP_060390.3
	URGCP	NM_001077664.3		c.1885G>A	p.Val629Ile	missense	Exon 6 of 6	NP_001071132.1	Q8TCY9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URGCP	ENST00000453200.6	TSL:1 MANE Select	c.2014G>A	p.Val672Ile	missense	Exon 6 of 6	ENSP00000396918.1	Q8TCY9-1
	URGCP	ENST00000402306.7	TSL:1	c.1987G>A	p.Val663Ile	missense	Exon 5 of 5	ENSP00000384955.3	Q8TCY9-2
	URGCP	ENST00000336086.10	TSL:1	c.1885G>A	p.Val629Ile	missense	Exon 4 of 4	ENSP00000336872.6	Q8TCY9-4

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000100 AC: 25 AN: 248768 AF XY: 0.0000666

Gnomad AFR exome AF: 0.000583

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000472

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1461288 Hom.: 1 Cov.: 92 AF XY: 0.0000564 AC XY: 41 AN XY: 727004

African (AFR) AF: 0.00116 AC: 39 AN: 33478

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52922

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111934

Other (OTH) AF: 0.000315 AC: 19 AN: 60382

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152296 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74474

African (AFR) AF: 0.000770 AC: 32 AN: 41564

American (AMR) AF: 0.000327 AC: 5 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000196 Hom.: 0

Bravo AF: 0.000283

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000472 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000124 AC: 15

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.088
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.14
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.016
Sift	Benign	0.12	T
Sift4G	Uncertain	0.037	D
Polyphen		0.0050	B
Vest4		0.031
MVP		0.055
MPC		0.40
ClinPred		0.0020	T
GERP RS		0.40
Varity_R		0.019
gMVP		0.094
Mutation Taster		=98/2	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: rs201208471; hg19: chr7-43917048; COSMIC: COSV56246241; COSMIC: COSV56246241;