Variant 2-241686681-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012145.4(DTYMK):c.103C>T(p.His35Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000677 in 1,530,462 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00091 ( 3 hom., cov: 34)

Exomes 𝑓: 0.00065 ( 9 hom. )

Consequence

DTYMK
NM_012145.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

DTYMK (HGNC:3061): (deoxythymidylate kinase) Enables thymidylate kinase activity. Predicted to be involved in dTDP biosynthetic process; dTTP biosynthetic process; and dUDP biosynthetic process. Predicted to act upstream of or within cellular response to growth factor stimulus and nucleotide biosynthetic process. Predicted to be located in mitochondrial intermembrane space and mitochondrial matrix. Predicted to be active in cytosol; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DTYMK links:

DTYMK (HGNC:):

DTYMK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046788156).

BP6

Variant 2-241686681-G-A is Benign according to our data. Variant chr2-241686681-G-A is described in ClinVar as [Benign]. Clinvar id is 730030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000913 (139/152252) while in subpopulation EAS AF= 0.0259 (134/5182). AF 95% confidence interval is 0.0223. There are 3 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTYMK	NM_012145.4 linkuse as main transcript	c.103C>T	p.His35Tyr	missense_variant	1/5	ENST00000305784.7	NP_036277.2	P23919-1Q6FGU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTYMK	ENST00000305784.7 linkuse as main transcript	c.103C>T	p.His35Tyr	missense_variant	1/5	1	NM_012145.4	ENSP00000304802.2		P23919-1

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00226

AC:

293

AN:

129698

Hom.:

AF XY:

0.00211

AC XY:

155

AN XY:

73424

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0328

Gnomad SAS exome

AF:

0.0000895

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.000277

GnomAD4 exome

AF:

0.000651

AC:

897

AN:

1378210

Hom.:

Cov.:

AF XY:

0.000636

AC XY:

434

AN XY:

682508

show subpopulations

Gnomad4 AFR exome

AF:

0.0000702

Gnomad4 AMR exome

AF:

0.0000867

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0243

Gnomad4 SAS exome

AF:

0.0000885

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000647

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000913

AC:

139

AN:

152252

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0259

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000276

Hom.:

Bravo

AF:

0.00103

ExAC

AF:

0.00153

AC:

168

Asia WGS

AF:

0.00404

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.12

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.4

REVEL

Benign

0.071

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.19

MVP

0.12

MPC

0.32

ClinPred

0.038

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.72

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