rs34743033

Variant names:

• chr18-657657-GGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC-CGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG
• rs34743033
• NM_001071.4:c.-86_-13delGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCCinsCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG

Your query was ambiguous. Multiple possible variants found:

• chr18-657656-TGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC-TCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG
• chr18-657656-TGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC-TCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG
• chr18-657656-TGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC-TCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001071.4(TYMS):​c.-86_-13delGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCCinsCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: TYMS NM_001071.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 89 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYMS	NM_001071.4	c.-86_-13delGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCCinsCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG		5_prime_UTR_variant	Exon 1 of 7	ENST00000323274.15	NP_001062.1
TYMS	NM_001354867.2	c.-86_-13delGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCCinsCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG		5_prime_UTR_variant	Exon 1 of 6		NP_001341796.1
TYMS	NM_001354868.2	c.-86_-13delGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCCinsCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG		5_prime_UTR_variant	Exon 1 of 5		NP_001341797.1
TYMSOS	NR_171001.1	n.450+112_450+185delGGGGGACGGAGGCAGGCGAAGTGGCGCGGCGGGACGGAGGCAGGCCAAGTGGCGCGGCGGGACGGAGGCAGGCCinsCGGGACGGAGGCAGGCGAAGTGGCGCGGCGGGACGGAGGCAGGCG		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYMS	ENST00000323274.15	c.-86_-13delGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCCinsCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCG		5_prime_UTR_variant	Exon 1 of 7	1	NM_001071.4	ENSP00000315644.10

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

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

Other links and lift over

dbSNP: rs34743033; hg19: chr18-657657;