6-29487260-A-G

Position:

• chr6-29487260-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052967.2(MAS1L):​c.643T>C​(p.Trp215Arg) 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. 14/21 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: MAS1L NM_052967.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.311

Genes affected

MAS1L (HGNC:13961): (MAS1 proto-oncogene like, G protein-coupled receptor) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289203 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20473933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAS1L	NM_052967.2	c.643T>C	p.Trp215Arg	missense_variant	1/1	ENST00000377127.4	NP_443199.1
LOC105375008	XR_007059916.1	n.394+2097A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAS1L	ENST00000377127.4	c.643T>C	p.Trp215Arg	missense_variant	1/1	6	NM_052967.2	ENSP00000366331.3
ENSG00000289203	ENST00000688607.1	n.1583+247T>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.643T>C (p.W215R) alteration is located in exon 1 (coding exon 1) of the MAS1L gene. This alteration results from a T to C substitution at nucleotide position 643, causing the tryptophan (W) at amino acid position 215 to be replaced by an arginine (R). 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	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.44
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00088	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.041
Sift	Benign	0.091	T
Sift4G	Benign	0.37	T
Polyphen		0.012	B
Vest4		0.30
MutPred		0.69		Gain of methylation at W215 (P = 0.0393);
MVP		0.10
MPC		0.46
ClinPred		0.048	T
GERP RS		-4.2
Varity_R		0.084
gMVP		0.062

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-29455037;