Variant 14-23989045-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198083.4(DHRS4L2):c.98A>T(p.Lys33Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000313 in 1,595,644 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

DHRS4L2
NM_198083.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

DHRS4L2 (HGNC:19731): (dehydrogenase/reductase 4 like 2) This gene encodes a member of the short chain dehydrogenase reductase family. The encoded protein may be an NADPH dependent retinol oxidoreductase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

DHRS4L2 links:

DHRS4-AS1 (HGNC:):

DHRS4-AS1 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
DHRS4L2	NM_198083.4 linkuse as main transcript	c.98A>T	p.Lys33Met	missense_variant	1/8	ENST00000335125.11	NP_932349.2	Q6PKH6-1D5KJA1
DHRS4L2	NM_001193635.1 linkuse as main transcript	c.45-1137A>T		intron_variant			NP_001180564.1	D5KJA1
DHRS4L2	NM_001193636.1 linkuse as main transcript	c.-175-1137A>T		intron_variant			NP_001180565.1	D5KJA2A0A087WSZ6D5KJA1
DHRS4L2	NM_001193637.1 linkuse as main transcript	c.-175-1137A>T		intron_variant			NP_001180566.1	D5KJA1F6VUV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS4L2	ENST00000335125.11 linkuse as main transcript	c.98A>T	p.Lys33Met	missense_variant	1/8	1	NM_198083.4	ENSP00000334801.6		Q6PKH6-1

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000726

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000510

AC:

AN:

215718

Hom.:

AF XY:

0.0000344

AC XY:

AN XY:

116228

show subpopulations

Gnomad AFR exome

AF:

0.000773

Gnomad AMR exome

AF:

0.0000327

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1443954

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

716564

show subpopulations

Gnomad4 AFR exome

AF:

0.000453

Gnomad4 AMR exome

AF:

0.0000479

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:

0.00

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.000198

AC:

AN:

151690

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.000726

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.0000414

AC:

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

Oct 05, 2023

The c.98A>T (p.K33M) alteration is located in exon 1 (coding exon 1) of the DHRS4L2 gene. This alteration results from a A to T substitution at nucleotide position 98, causing the lysine (K) at amino acid position 33 to be replaced by a methionine (M). 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

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;.;.;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

D;D;.;.;D

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.55

D;D;D;D;D

MetaSVM

Uncertain

0.73

PROVEAN

Pathogenic

-4.5

D;D;D;D;D

REVEL

Uncertain

0.50

Sift

Pathogenic

0.0

D;D;D;T;T

Sift4G

Uncertain

0.036

D;D;D;D;D

Polyphen

1.0

.;.;.;D;D

Vest4

0.71

MVP

0.90

MPC

0.30

ClinPred

0.63

GERP RS

2.8

gMVP

0.81

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