Variant 18-662247-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001071.4(TYMS):c.381A>G(p.Glu127Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,613,976 control chromosomes in the GnomAD database, including 973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 119 hom., cov: 32)

Exomes 𝑓: 0.011 ( 854 hom. )

Consequence

TYMS
NM_001071.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.686

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]

TYMS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 18-662247-A-G is Benign according to our data. Variant chr18-662247-A-G is described in ClinVar as [Benign]. Clinvar id is 3038406.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.686 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYMS	NM_001071.4 link	c.381A>G	p.Glu127Glu	synonymous_variant	Exon 3 of 7	ENST00000323274.15	NP_001062.1	P04818-1Q53Y97
TYMS	NM_001354867.2 link	c.381A>G	p.Glu127Glu	synonymous_variant	Exon 3 of 6		NP_001341796.1
TYMS	NM_001354868.2 link	c.205+4300A>G		intron_variant	Intron 1 of 4		NP_001341797.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TYMS	ENST00000323274.15 link	c.381A>G	p.Glu127Glu	synonymous_variant	Exon 3 of 7	1	NM_001071.4	ENSP00000315644.10	P04818-1
TYMS	ENST00000323224.7 link	c.381A>G	p.Glu127Glu	synonymous_variant	Exon 3 of 6	1		ENSP00000314727.7	P04818-2
TYMS	ENST00000323250.9 link	c.205+4300A>G		intron_variant	Intron 1 of 4	1		ENSP00000314902.5	P04818-3
TYMS	ENST00000579128.1 link	n.459A>G		non_coding_transcript_exon_variant	Exon 3 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1790

AN:

152178

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.0846

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00908

GnomAD3 exomes

AF:

0.0298

AC:

7475

AN:

251258

Hom.:

372

AF XY:

0.0297

AC XY:

4030

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.0624

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.0799

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000448

Gnomad OTH exome

AF:

0.0137

GnomAD4 exome

AF:

0.0109

AC:

15931

AN:

1461678

Hom.:

854

Cov.:

AF XY:

0.0126

AC XY:

9161

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.0563

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.0762

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0117

AC:

1787

AN:

152298

Hom.:

119

Cov.:

AF XY:

0.0141

AC XY:

1048

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.0314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.0845

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00450

Hom.:

Bravo

AF:

0.0141

Asia WGS

AF:

0.111

AC:

386

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TYMS-related disorder

Benign:1

Oct 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

5.6

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over