chr6-29487287-T-A

Variant names:

• chr6-29487287-T-A
• rs1386417351
• NM_052967.2:c.616A>T

Variant summary

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

The NM_052967.2(MAS1L):​c.616A>T​(p.Ile206Leu) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I206T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAS1L NM_052967.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 0 publications found

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

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=0.08550057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052967.2. 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
	MAS1L	NM_052967.2	MANE Select	c.616A>T	p.Ile206Leu	missense	Exon 1 of 1	NP_443199.1	P35410

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAS1L	ENST00000377127.4	TSL:6 MANE Select	c.616A>T	p.Ile206Leu	missense	Exon 1 of 1	ENSP00000366331.3	P35410
	ENSG00000289203	ENST00000688607.1		n.1583+220A>T		intron	N/A
	ENSG00000299453	ENST00000763658.1		n.508+2124T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.7
DANN	Benign	0.74
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0021	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.010
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.044
Sift	Benign	0.30	T
Sift4G	Benign	0.42	T
Polyphen		0.041	B
Vest4		0.16
MutPred		0.45		Loss of methylation at K208 (P = 0.0554)
MVP		0.23
MPC		0.071
ClinPred		0.12	T
GERP RS		-0.79
Varity_R		0.050
gMVP		0.059
Mutation Taster		=98/2	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

dbSNP: rs1386417351; hg19: chr6-29455064;