NM_001085049.3:c.16G>T

Variant names:

• chr3-138372899-G-T
• NM_001085049.3:c.16G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001085049.3(MRAS):​c.16G>T​(p.Val6Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MRAS NM_001085049.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.00

Genes affected

MRAS (HGNC:7227): (muscle RAS oncogene homolog) This gene encodes a member of the Ras family of small GTPases. These membrane-associated proteins function as signal transducers in multiple processes including cell growth and differentiation, and dysregulation of Ras signaling has been associated with many types of cancer. The encoded protein may play a role in the tumor necrosis factor-alpha and MAP kinase signaling pathways. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38762248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRAS	NM_001085049.3	c.16G>T	p.Val6Phe	missense_variant	Exon 2 of 6	ENST00000423968.7	NP_001078518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRAS	ENST00000423968.7	c.16G>T	p.Val6Phe	missense_variant	Exon 2 of 6	1	NM_001085049.3	ENSP00000389682.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1392014 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 691168

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: 0.00

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	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T;T;T;T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	.;.;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.63	N;N;.;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.34	N;N;D;N
REVEL	Benign	0.23
Sift	Benign	0.15	T;T;.;T
Sift4G	Uncertain	0.050	T;T;D;T
Polyphen		0.30	B;B;.;B
Vest4		0.59
MutPred		0.22		Loss of glycosylation at T3 (P = 0.0104);Loss of glycosylation at T3 (P = 0.0104);Loss of glycosylation at T3 (P = 0.0104);Loss of glycosylation at T3 (P = 0.0104);
MVP		0.72
MPC		1.5
ClinPred		0.59	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-138091741;