11-75815413-C-T

Variant names:

• chr11-75815413-C-T
• rs915161693
• NM_003369.4:c.6C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003369.4(UVRAG):​c.6C>T​(p.Ser2Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UVRAG NM_003369.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.973
• Publications: 0 publications found

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]

UVRAG-DT (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP7: Synonymous conserved (PhyloP=0.973 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003369.4. 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
	UVRAG	NM_003369.4	MANE Select	c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 15	NP_003360.2
	UVRAG	NM_001386671.1		c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 16	NP_001373600.1
	UVRAG	NM_001386672.1		c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 14	NP_001373601.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UVRAG	ENST00000356136.8	TSL:1 MANE Select	c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 15	ENSP00000348455.3	Q9P2Y5-1
	UVRAG	ENST00000876952.1		c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 16	ENSP00000547011.1
	UVRAG	ENST00000969466.1		c.6C>T	p.Ser2Ser	synonymous	Exon 1 of 15	ENSP00000639525.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1094394 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 520650

African (AFR) AF: 0.00 AC: 0 AN: 22954

American (AMR) AF: 0.00 AC: 0 AN: 8474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14568

East Asian (EAS) AF: 0.00 AC: 0 AN: 26630

South Asian (SAS) AF: 0.00 AC: 0 AN: 26704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3230

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 925624

Other (OTH) AF: 0.00 AC: 0 AN: 44134

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2090

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		0.97
PromoterAI		0.0045	Neutral

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: rs915161693; hg19: chr11-75526458;