6-159907544-C-G

Variant names:

• chr6-159907544-C-G
• NM_002377.4:c.589C>G

Variant summary

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

The NM_002377.4(MAS1):​c.589C>G​(p.Leu197Val) 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: 32)
• Consequence: MAS1 NM_002377.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.812
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18052733).

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.589C>G	p.Leu197Val	missense	Exon 3 of 3	NP_002368.1	P04201
	MAS1	NM_001366704.2		c.589C>G	p.Leu197Val	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.589C>G	p.Leu197Val	missense	Exon 3 of 3	ENSP00000501180.2	P04201
	MAS1	ENST00000252660.5	TSL:6	c.589C>G	p.Leu197Val	missense	Exon 1 of 1	ENSP00000252660.4	P04201

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.13
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.28	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.81
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.19
Sift	Benign	0.054	T
Sift4G	Benign	0.092	T
Polyphen		0.45	B
Vest4		0.11
MutPred		0.53		Gain of catalytic residue at L197 (P = 0.0648)
MVP		0.55
MPC		0.14
ClinPred		0.39	T
GERP RS		2.4
Varity_R		0.15
gMVP		0.39
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

hg19: chr6-160328576;