Menu
GeneBe

rs33917957

Variant summary

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

The NM_000245.4(MET):c.1124A>C(p.Asn375Thr) 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. 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. N375K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

MET
NM_000245.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.92
Variant links:
Genes affected
MET (HGNC:7029): (MET proto-oncogene, receptor tyrosine kinase) This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

Genome browser will be placed here

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=0.27962667).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
METNM_000245.4 linkuse as main transcriptc.1124A>C p.Asn375Thr missense_variant 2/21 ENST00000397752.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
METENST00000397752.8 linkuse as main transcriptc.1124A>C p.Asn375Thr missense_variant 2/211 NM_000245.4 P3P08581-1
METENST00000318493.11 linkuse as main transcriptc.1124A>C p.Asn375Thr missense_variant 2/211 A2P08581-2
METENST00000436117.3 linkuse as main transcriptc.1124A>C p.Asn375Thr missense_variant, NMD_transcript_variant 2/201 P08581-3
METENST00000422097.2 linkuse as main transcriptc.1124A>C p.Asn375Thr missense_variant 2/123

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
Cadd
Benign
23
Dann
Uncertain
0.99
DEOGEN2
Benign
0.32
T;.;.
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L;L
MutationTaster
Benign
0.77
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.0
N;N;N
REVEL
Benign
0.14
Sift
Benign
0.036
D;D;T
Sift4G
Benign
0.097
T;T;D
Polyphen
0.63
P;B;.
Vest4
0.50
MutPred
0.36
Gain of MoRF binding (P = 0.1323);Gain of MoRF binding (P = 0.1323);Gain of MoRF binding (P = 0.1323);
MVP
0.42
MPC
0.56
ClinPred
0.80
D
GERP RS
4.9
Varity_R
0.34
gMVP
0.49

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: chr7-116340262; API