GeneBe

rs45445694

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The 18-657645-ACCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCG-A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000887 in 1,002,936 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

TYMS
NM_001071.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.424
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TYMSNM_001071.4 linkuse as main transcript 5_prime_UTR_variant 1/7 ENST00000323274.15
TYMSOSNR_171001.1 linkuse as main transcriptn.450+141_450+196del intron_variant, non_coding_transcript_variant
TYMSNM_001354867.2 linkuse as main transcript 5_prime_UTR_variant 1/6
TYMSNM_001354868.2 linkuse as main transcript 5_prime_UTR_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TYMSENST00000323274.15 linkuse as main transcript 5_prime_UTR_variant 1/71 NM_001071.4 P1P04818-1
TYMSOSENST00000585033.1 linkuse as main transcriptn.428+141_428+196del intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000108
AC:
16
AN:
148234
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.000176
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000135
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000854
AC:
73
AN:
854598
Hom.:
0
AF XY:
0.0000833
AC XY:
35
AN XY:
420322
show subpopulations
Gnomad4 AFR exome
AF:
0.000246
Gnomad4 AMR exome
AF:
0.000267
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000908
Gnomad4 OTH exome
AF:
0.0000843
GnomAD4 genome
AF:
0.000108
AC:
16
AN:
148338
Hom.:
0
Cov.:
0
AF XY:
0.0000967
AC XY:
7
AN XY:
72410
show subpopulations
Gnomad4 AFR
AF:
0.000175
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000135
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs45445694; hg19: chr18-657645; API