chr7-130498199-C-A

Position:

• chr7-130498199-C-A

Variant summary

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

The NM_002402.4(MEST):​c.400C>A​(p.Leu134Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEST NM_002402.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518

Genes affected

MEST (HGNC:7028): (mesoderm specific transcript) This gene encodes a member of the alpha/beta hydrolase superfamily. It is imprinted, exhibiting preferential expression from the paternal allele in fetal tissues, and isoform-specific imprinting in lymphocytes. The loss of imprinting of this gene has been linked to certain types of cancer and may be due to promotor switching. The encoded protein may play a role in development. Alternatively spliced transcript variants encoding multiple isoforms have been identified for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3 and 4, and the long arm of chromosomes 6 and 15. [provided by RefSeq, Dec 2011]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEST	NM_002402.4	c.400C>A	p.Leu134Met	missense_variant	5/12	ENST00000223215.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEST	ENST00000223215.10	c.400C>A	p.Leu134Met	missense_variant	5/12	1	NM_002402.4
	ENST00000604666.1	n.229G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	.;.;.;.;T;.;T;T;.;.;.;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.050
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.93	.;.;.;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.2	.;.;.;.;.;.;.;M;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;N;N;.;.;N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0060	D;D;D;D;D;D;D;D;.;.;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D;D;D;D;.;.;D;D
Polyphen		1.0	.;D;D;D;.;.;.;D;.;.;.;.
Vest4		0.67
MutPred		0.80		.;.;.;.;.;.;.;Loss of helix (P = 0.1299);.;.;.;.;
MVP		0.64
MPC		2.0
ClinPred		0.88	D
GERP RS		3.5
Varity_R		0.22
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs61735155; hg19: chr7-130138040;