6-159907112-C-T

Variant names:

• chr6-159907112-C-T
• NM_002377.4:c.157C>T

Variant summary

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

The NM_002377.4(MAS1):​c.157C>T​(p.Leu53Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAS1 NM_002377.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18
• 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=0.31363228).

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.157C>T	p.Leu53Phe	missense	Exon 3 of 3	NP_002368.1	P04201
	MAS1	NM_001366704.2		c.157C>T	p.Leu53Phe	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.157C>T	p.Leu53Phe	missense	Exon 3 of 3	ENSP00000501180.2	P04201
	MAS1	ENST00000252660.5	TSL:6	c.157C>T	p.Leu53Phe	missense	Exon 1 of 1	ENSP00000252660.4	P04201

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.62	P
Vest4		0.29
MutPred		0.57		Loss of sheet (P = 0.0817)
MVP		0.85
MPC		0.49
ClinPred		0.93	D
GERP RS		4.8
PromoterAI		-0.014	Neutral
Varity_R		0.28
gMVP		0.54
Mutation Taster		=88/12	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: chr6-160328144;