11-75815510-C-A

Variant names:

• chr11-75815510-C-A
• rs1323348747
• NM_003369.4:c.103C>A

Variant summary

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

The NM_003369.4(UVRAG):​c.103C>A​(p.Leu35Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UVRAG NM_003369.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66
• 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: 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=0.28113782).

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.103C>A	p.Leu35Met	missense	Exon 1 of 15	NP_003360.2
	UVRAG	NM_001386671.1		c.103C>A	p.Leu35Met	missense	Exon 1 of 16	NP_001373600.1
	UVRAG	NM_001386672.1		c.103C>A	p.Leu35Met	missense	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.103C>A	p.Leu35Met	missense	Exon 1 of 15	ENSP00000348455.3	Q9P2Y5-1
	UVRAG	ENST00000876952.1		c.103C>A	p.Leu35Met	missense	Exon 1 of 16	ENSP00000547011.1
	UVRAG	ENST00000969466.1		c.103C>A	p.Leu35Met	missense	Exon 1 of 15	ENSP00000639525.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152144 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: 1086832 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 514892

African (AFR) AF: 0.00 AC: 0 AN: 22990

American (AMR) AF: 0.00 AC: 0 AN: 8408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14450

East Asian (EAS) AF: 0.00 AC: 0 AN: 26616

South Asian (SAS) AF: 0.00 AC: 0 AN: 23298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2934

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 922794

Other (OTH) AF: 0.00 AC: 0 AN: 43856

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.80
BayesDel_addAF	Benign	0.0054	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.038
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.0	L
PhyloP100		2.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.43
MutPred		0.24		Loss of helix (P = 0.0237)
MVP		0.068
MPC		0.95
ClinPred		0.93	D
GERP RS		3.0
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.42
Mutation Taster		=80/20	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: rs1323348747; hg19: chr11-75526555;