NM_003369.4:c.374A>C

Variant names:

• chr11-75879982-A-C
• NM_003369.4:c.374A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003369.4(UVRAG):​c.374A>C​(p.Tyr125Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UVRAG NM_003369.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

UVRAG (HGNC:12640): (UV radiation resistance associated) This gene complements the ultraviolet sensitivity of xeroderma pigmentosum group C cells and encodes a protein with a C2 domain. The protein activates the Beclin1-PI(3)KC3 complex, promoting autophagy and suppressing the proliferation and tumorigenicity of human colon cancer cells. Chromosomal aberrations involving this gene are associated with left-right axis malformation and mutations in this gene have been associated with colon cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23942593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UVRAG	NM_003369.4	c.374A>C	p.Tyr125Ser	missense_variant	Exon 4 of 15	ENST00000356136.8	NP_003360.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UVRAG	ENST00000356136.8	c.374A>C	p.Tyr125Ser	missense_variant	Exon 4 of 15	1	NM_003369.4	ENSP00000348455.3
UVRAG	ENST00000528420.5	c.71A>C	p.Tyr24Ser	missense_variant	Exon 4 of 15	2		ENSP00000436039.1
UVRAG	ENST00000528264.1	c.71A>C	p.Tyr24Ser	missense_variant	Exon 2 of 5	5		ENSP00000433613.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461856 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.14	T;T;T
Eigen	Benign	-0.025
Eigen_PC	Benign	0.051
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.4	N;N;D
REVEL	Benign	0.23
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.077	T;D;D
Polyphen		0.72	P;.;.
Vest4		0.70
MutPred		0.60		Loss of ubiquitination at K121 (P = 0.1498);.;.;
MVP		0.62
MPC		0.61
ClinPred		0.36	T
GERP RS		3.2
Varity_R		0.091
gMVP		0.77

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: chr11-75591026;