Variant 2-241685863-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012145.4(DTYMK):c.145A>C(p.Ile49Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

DTYMK
NM_012145.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95

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 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	Protein	UniProt
DTYMK	NM_012145.4 linkuse as main transcript	c.145A>C	p.Ile49Leu	missense_variant	2/5	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.145A>C	p.Ile49Leu	missense_variant	2/5	1	NM_012145.4	ENSP00000304802.2		P23919-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251450

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000280

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.145A>C (p.I49L) alteration is located in exon 2 (coding exon 2) of the DTYMK gene. This alteration results from a A to C substitution at nucleotide position 145, causing the isoleucine (I) at amino acid position 49 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.82

M_CAP

Benign

0.0071

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.32

Sift

Uncertain

0.012

Sift4G

Uncertain

0.014

Polyphen

0.63

Vest4

0.57

MutPred

0.75

Gain of disorder (P = 0.0393);

MVP

0.24

MPC

0.34

ClinPred

0.32

GERP RS

4.2

Varity_R

0.82

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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