6-159907241-G-C

Variant names:

• chr6-159907241-G-C
• NM_002377.4:c.286G>C

Variant summary

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

The NM_002377.4(MAS1):​c.286G>C​(p.Glu96Gln) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAS1 NM_002377.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• Publications: 0 publications found

Genes affected

MAS1 (HGNC:6899): (MAS1 proto-oncogene, G protein-coupled receptor) This gene encodes a class I seven-transmembrane G-protein-coupled receptor. The encoded protein is a receptor for angiotensin-(1-7) and preferentially couples to the Gq protein, activating the phospholipase C signaling pathway. The encoded protein may play a role in multiple processes including hypotension, smooth muscle relaxation and cardioprotection by mediating the effects of angiotensin-(1-7). [provided by RefSeq, May 2012]

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=0.332185).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002377.4. 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
	MAS1	NM_002377.4	MANE Select	c.286G>C	p.Glu96Gln	missense	Exon 3 of 3	NP_002368.1	P04201
	MAS1	NM_001366704.2		c.286G>C	p.Glu96Gln	missense	Exon 2 of 2	NP_001353633.1	P04201

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAS1	ENST00000674077.2	MANE Select	c.286G>C	p.Glu96Gln	missense	Exon 3 of 3	ENSP00000501180.2	P04201
	MAS1	ENST00000252660.5	TSL:6	c.286G>C	p.Glu96Gln	missense	Exon 1 of 1	ENSP00000252660.4	P04201

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	Benign	0.093
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	0.010
Eigen_PC	Benign	-0.0028
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.20	N
PhyloP100		2.7
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.22
Sift	Benign	0.12	T
Sift4G	Benign	0.51	T
Polyphen		0.94	P
Vest4		0.20
MutPred		0.26		Loss of glycosylation at S98 (P = 0.1432)
MVP		0.86
MPC		0.15
ClinPred		0.55	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.41
Mutation Taster		=94/6	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

hg19: chr6-160328273;