chr6-159907112-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.31363228).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAS1NM_002377.4 linkc.157C>T p.Leu53Phe missense_variant Exon 3 of 3 ENST00000674077.2 NP_002368.1 P04201W8W3P4
MAS1NM_001366704.2 linkc.157C>T p.Leu53Phe missense_variant Exon 2 of 2 NP_001353633.1
MAS1XM_047418776.1 linkc.157C>T p.Leu53Phe missense_variant Exon 4 of 4 XP_047274732.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAS1ENST00000674077.2 linkc.157C>T p.Leu53Phe missense_variant Exon 3 of 3 NM_002377.4 ENSP00000501180.2 P04201
MAS1ENST00000252660.5 linkc.157C>T p.Leu53Phe missense_variant Exon 1 of 1 6 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
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.157C>T (p.L53F) alteration is located in exon 1 (coding exon 1) of the MAS1 gene. This alteration results from a C to T substitution at nucleotide position 157, causing the leucine (L) at amino acid position 53 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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
Varity_R
0.28
gMVP
0.54

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-160328144; API