Genetic Variant ENST00000323813.6:n.511+368A>G (chr18-657474-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000323813.6(TYMSOS):n.511+368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 272,772 control chromosomes in the GnomAD database, including 10,597 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.26 ( 5395 hom., cov: 31)

Exomes 𝑓: 0.29 ( 5202 hom. )

Consequence

TYMSOS
ENST00000323813.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

Publications

7 publications found

Variant links:

Genes affected

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

TYMSOS links:

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]

TYMS links:

ENSG00000263727 (HGNC:):

ENSG00000263727 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TYMSOS	NR_171001.1 link	n.450+368A>G	intron_variant	Intron 1 of 1
TYMS	NM_001071.4 link	c.-269T>C	upstream_gene_variant		ENST00000323274.15	NP_001062.1	P04818-1Q53Y97
TYMS	NM_001354867.2 link	c.-269T>C	upstream_gene_variant			NP_001341796.1
TYMS	NM_001354868.2 link	c.-269T>C	upstream_gene_variant			NP_001341797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYMS	ENST00000323274.15 link	c.-269T>C		upstream_gene_variant		1	NM_001071.4	ENSP00000315644.10		P04818-1

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40114

AN:

151900

Hom.:

5393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.289

AC:

34839

AN:

120754

Hom.:

5202

AF XY:

0.289

AC XY:

17937

AN XY:

62038

show subpopulations

African (AFR)

AF:

0.241

AC:

757

AN:

3142

American (AMR)

AF:

0.300

AC:

1009

AN:

3364

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

1286

AN:

4336

East Asian (EAS)

AF:

0.179

AC:

1559

AN:

8710

South Asian (SAS)

AF:

0.279

AC:

321

AN:

1150

European-Finnish (FIN)

AF:

0.375

AC:

4401

AN:

11730

Middle Eastern (MID)

AF:

0.189

AC:

122

AN:

644

European-Non Finnish (NFE)

AF:

0.291

AC:

23251

AN:

79906

Other (OTH)

AF:

0.274

AC:

2133

AN:

7772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

1128

2255

3383

4510

5638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.264

AC:

40141

AN:

152018

Hom.:

5395

Cov.:

AF XY:

0.267

AC XY:

19833

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.236

AC:

9792

AN:

41484

American (AMR)

AF:

0.264

AC:

4032

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3466

East Asian (EAS)

AF:

0.143

AC:

736

AN:

5140

South Asian (SAS)

AF:

0.253

AC:

1218

AN:

4810

European-Finnish (FIN)

AF:

0.362

AC:

3832

AN:

10578

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18767

AN:

67940

Other (OTH)

AF:

0.256

AC:

541

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1525

3050

4576

6101

7626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.273

Hom.:

1270

Bravo

AF:

0.258

Asia WGS

AF:

0.184

AC:

642

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.3

(source)

DANN

Benign

0.65

PhyloP100

1.5

PromoterAI

-0.0059

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000323813.6:n.511+368A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over