7-43876690-T-G

Position:

• chr7-43876690-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001077663.3(URGCP):​c.2773A>C​(p.Ile925Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.00065 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: URGCP NM_001077663.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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]

URGCP (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13852191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
URGCP	NM_001077663.3	c.2773A>C	p.Ile925Leu	missense_variant	6/6	ENST00000453200.6	NP_001071131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
URGCP	ENST00000453200.6	c.2773A>C	p.Ile925Leu	missense_variant	6/6	1	NM_001077663.3	ENSP00000396918.1
URGCP-MRPS24	ENST00000603700.1	c.175+4969A>C		intron_variant		5		ENSP00000473871.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000645 AC: 940 AN: 1456996 Hom.: 0 Cov.: 31 AF XY: 0.000595 AC XY: 431 AN XY: 724948

Gnomad4 AFR exome AF: 0.000479

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000783

Gnomad4 OTH exome AF: 0.000498

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

The c.2773A>C (p.I925L) alteration is located in exon 6 (coding exon 6) of the URGCP gene. This alteration results from a A to C substitution at nucleotide position 2773, causing the isoleucine (I) at amino acid position 925 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	.;.;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	.;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;.;.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.41	N;N;N;N
REVEL	Benign	0.070
Sift	Benign	0.25	T;T;T;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.055	.;B;.;B
Vest4		0.20
MutPred		0.47		.;.;.;Gain of disorder (P = 0.0627);
MVP		0.061
MPC		0.68
ClinPred		0.54	D
GERP RS		4.1
Varity_R		0.080
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-43916289;