11-75911978-A-C

Variant names:

• chr11-75911978-A-C
• rs868707282
• NM_003369.4:c.532A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003369.4(UVRAG):​c.532A>C​(p.Ile178Leu) 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. 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. I178V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UVRAG NM_003369.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08390108).

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.532A>C	p.Ile178Leu	missense	Exon 6 of 15	NP_003360.2
	UVRAG	NM_001386671.1		c.532A>C	p.Ile178Leu	missense	Exon 6 of 16	NP_001373600.1
	UVRAG	NM_001386672.1		c.370A>C	p.Ile124Leu	missense	Exon 5 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.532A>C	p.Ile178Leu	missense	Exon 6 of 15	ENSP00000348455.3	Q9P2Y5-1
	UVRAG	ENST00000876952.1		c.532A>C	p.Ile178Leu	missense	Exon 6 of 16	ENSP00000547011.1
	UVRAG	ENST00000969466.1		c.532A>C	p.Ile178Leu	missense	Exon 6 of 15	ENSP00000639525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.067
Sift	Benign	0.25	T
Sift4G	Benign	0.39	T
Polyphen		0.0050	B
Vest4		0.23
MutPred		0.34		Loss of helix (P = 0.0104)
MVP		0.068
MPC		0.28
ClinPred		0.32	T
GERP RS		3.0
Varity_R		0.067
gMVP		0.24
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs868707282; hg19: chr11-75623022;