chr6-29486780-C-A

Variant names:

• chr6-29486780-C-A
• rs141618302
• NM_052967.2:c.1123G>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.1123G>T​(p.Asp375Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. D375N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAS1L NM_052967.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• 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=0.09231052).

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.1123G>T	p.Asp375Tyr	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.1123G>T	p.Asp375Tyr	missense	Exon 1 of 1	ENSP00000366331.3	P35410
	ENSG00000289203	ENST00000688607.1		n.1583+727G>T		intron	N/A
	ENSG00000299453	ENST00000763658.1		n.508+1617C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459322 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725786

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110952

Other (OTH) AF: 0.00 AC: 0 AN: 60284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.59
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0038	N
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.54
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D
Polyphen		0.66	P
Vest4		0.13
MutPred		0.24		Gain of phosphorylation at D375 (P = 0.0276)
MVP		0.030
MPC		0.10
ClinPred		0.13	T
GERP RS		-0.34
Varity_R		0.025
gMVP		0.20
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141618302; hg19: chr6-29454557;