18-657838-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_001071.4(TYMS):c.96G>A(p.Gln32=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000805 in 1,491,398 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
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
TYMS
NM_001071.4 synonymous
NM_001071.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.77
Genes affected
TYMS (HGNC:12441): (thymidylate synthetase) Thymidylate synthase catalyzes the methylation of deoxyuridylate to deoxythymidylate using, 10-methylenetetrahydrofolate (methylene-THF) as a cofactor. This function maintains the dTMP (thymidine-5-prime monophosphate) pool critical for DNA replication and repair. The enzyme has been of interest as a target for cancer chemotherapeutic agents. It is considered to be the primary site of action for 5-fluorouracil, 5-fluoro-2-prime-deoxyuridine, and some folate analogs. Expression of this gene and that of a naturally occurring antisense transcript, mitochondrial enolase superfamily member 1 (GeneID:55556), vary inversely when cell-growth progresses from late-log to plateau phase. Polymorphisms in this gene may be associated with etiology of neoplasia, including breast cancer, and response to chemotherapy. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 18-657838-G-A is Benign according to our data. Variant chr18-657838-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 762218.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYMS | NM_001071.4 | c.96G>A | p.Gln32= | synonymous_variant | 1/7 | ENST00000323274.15 | |
TYMSOS | NR_171001.1 | n.450+4C>T | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | ||||
TYMS | NM_001354867.2 | c.96G>A | p.Gln32= | synonymous_variant | 1/6 | ||
TYMS | NM_001354868.2 | c.96G>A | p.Gln32= | synonymous_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMS | ENST00000323274.15 | c.96G>A | p.Gln32= | synonymous_variant | 1/7 | 1 | NM_001071.4 | P1 | |
TYMSOS | ENST00000585033.1 | n.428+4C>T | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000747 AC: 10AN: 1339270Hom.: 0 Cov.: 31 AF XY: 0.00000606 AC XY: 4AN XY: 659608
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74320
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 05, 2018 | - - |
Computational scores
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Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at