rs1554399341

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000245.4(MET):ā€‹c.3300T>Cā€‹(p.Asn1100Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

MET
NM_000245.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.248
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 7-116777429-T-C is Benign according to our data. Variant chr7-116777429-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 524899.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.248 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
METNM_000245.4 linkuse as main transcriptc.3300T>C p.Asn1100Asn synonymous_variant 16/21 ENST00000397752.8 NP_000236.2 P08581-1A0A024R759
METNM_001127500.3 linkuse as main transcriptc.3354T>C p.Asn1118Asn synonymous_variant 16/21 NP_001120972.1 P08581-2A0A024R728
METNM_001324402.2 linkuse as main transcriptc.2010T>C p.Asn670Asn synonymous_variant 15/20 NP_001311331.1 B4DLF5
METXM_011516223.2 linkuse as main transcriptc.3357T>C p.Asn1119Asn synonymous_variant 17/22 XP_011514525.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
METENST00000397752.8 linkuse as main transcriptc.3300T>C p.Asn1100Asn synonymous_variant 16/211 NM_000245.4 ENSP00000380860.3 P08581-1
METENST00000318493.11 linkuse as main transcriptc.3354T>C p.Asn1118Asn synonymous_variant 16/211 ENSP00000317272.6 P08581-2
METENST00000436117.3 linkuse as main transcriptn.*905T>C non_coding_transcript_exon_variant 15/201 ENSP00000410980.2 P08581-3
METENST00000436117.3 linkuse as main transcriptn.*905T>C 3_prime_UTR_variant 15/201 ENSP00000410980.2 P08581-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461580
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 15, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
4.0
DANN
Benign
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554399341; hg19: chr7-116417483; API