18-657645-A-ACCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG

Position:

• chr18-657645-A-ACCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NR_171001.1(TYMSOS):​n.450+196_450+197insCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGG variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: TYMSOS NR_171001.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

Genes affected

TYMSOS (HGNC:29553): (TYMS opposite strand RNA)

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYMSOS	NR_171001.1	n.450+196_450+197insCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGG		intron_variant, non_coding_transcript_variant
TYMS	NM_001071.4			upstream_gene_variant		ENST00000323274.15
TYMS	NM_001354867.2			upstream_gene_variant
TYMS	NM_001354868.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYMSOS	ENST00000585033.1	n.428+196_428+197insCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGG		intron_variant, non_coding_transcript_variant		2
TYMS	ENST00000323274.15			upstream_gene_variant		1	NM_001071.4	P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45445694; hg19: chr18-657645;