rs73366471
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BS1BS2
The NM_001071.4(TYMS):c.205+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,521,696 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.014 ( 54 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 61 hom. )
Consequence
TYMS
NM_001071.4 intron
NM_001071.4 intron
Scores
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.307
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 Benign. Variant got -7 ACMG points.
PP3
?
BayesDel_noAF computational evidence supports a deleterious effect, 0.15
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2103/152320) while in subpopulation AFR AF= 0.0465 (1933/41576). AF 95% confidence interval is 0.0448. There are 54 homozygotes in gnomad4. There are 1033 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 52 Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TYMS | NM_001071.4 | c.205+54G>A | intron_variant | ENST00000323274.15 | |||
TYMSOS | NR_171001.1 | n.291C>T | non_coding_transcript_exon_variant | 1/2 | |||
TYMS | NM_001354867.2 | c.205+54G>A | intron_variant | ||||
TYMS | NM_001354868.2 | c.205+54G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TYMS | ENST00000323274.15 | c.205+54G>A | intron_variant | 1 | NM_001071.4 | P1 | |||
TYMSOS | ENST00000585033.1 | n.269C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0137 AC: 2084AN: 152202Hom.: 52 Cov.: 32
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GnomAD3 exomes AF: 0.00378 AC: 516AN: 136342Hom.: 16 AF XY: 0.00293 AC XY: 214AN XY: 72996
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GnomAD4 exome AF: 0.00151 AC: 2074AN: 1369376Hom.: 61 Cov.: 31 AF XY: 0.00134 AC XY: 905AN XY: 672982
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GnomAD4 genome ? AF: 0.0138 AC: 2103AN: 152320Hom.: 54 Cov.: 32 AF XY: 0.0139 AC XY: 1033AN XY: 74480
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at