7-116740983-C-T
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_000245.4(MET):c.1659C>T(p.Ser553Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,150 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 (★★).
Frequency
Consequence
NM_000245.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- hereditary papillary renal cell carcinomaInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- papillary renal cell carcinomaInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen
- autosomal recessive nonsyndromic hearing loss 97Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- osteofibrous dysplasiaInheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- arthrogryposis, distal, IIa 11Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- nonsyndromic genetic hearing lossInheritance: AR Classification: LIMITED Submitted by: ClinGen
- complex neurodevelopmental disorderInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.1659C>T | p.Ser553Ser | synonymous_variant | Exon 5 of 21 | ENST00000397752.8 | NP_000236.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000396 AC: 6AN: 151374Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000481 AC: 12AN: 249470 AF XY: 0.0000369 show subpopulations
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461776Hom.: 0 Cov.: 33 AF XY: 0.0000371 AC XY: 27AN XY: 727186 show subpopulations
GnomAD4 genome AF: 0.0000396 AC: 6AN: 151374Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 73846 show subpopulations
ClinVar
Submissions by phenotype
MET-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Renal cell carcinoma Benign:1
- -
Papillary renal cell carcinoma type 1 Benign:1
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
not provided Benign:1
- -
Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at