rs780354948

Variant names:

• chr7-43877371-C-A
• rs780354948
• NM_001077663.3:c.2092G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-43877371-C-A
• chr7-43877371-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077663.3(URGCP):​c.2092G>T​(p.Val698Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V698I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: URGCP NM_001077663.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27521747).

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.2092G>T	p.Val698Phe	missense	Exon 6 of 6	NP_001071131.1	Q8TCY9-1
	URGCP	NM_017920.5		c.2065G>T	p.Val689Phe	missense	Exon 5 of 5	NP_060390.3
	URGCP	NM_001077664.3		c.1963G>T	p.Val655Phe	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.2092G>T	p.Val698Phe	missense	Exon 6 of 6	ENSP00000396918.1	Q8TCY9-1
	URGCP	ENST00000402306.7	TSL:1	c.2065G>T	p.Val689Phe	missense	Exon 5 of 5	ENSP00000384955.3	Q8TCY9-2
	URGCP	ENST00000336086.10	TSL:1	c.1963G>T	p.Val655Phe	missense	Exon 4 of 4	ENSP00000336872.6	Q8TCY9-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460534 Hom.: 0 Cov.: 94 AF XY: 0.00 AC XY: 0 AN XY: 726676

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.14
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.011	B
Vest4		0.29
MutPred		0.39		Loss of MoRF binding (P = 0.0889)
MVP		0.21
MPC		0.67
ClinPred		0.62	D
GERP RS		4.0
Varity_R		0.098
gMVP		0.69
Mutation Taster		=77/23	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: rs780354948; hg19: chr7-43916970;