Genetic Variant DHRS7:p.Cys233Phe (chr14-60150123-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_016029.4(DHRS7):c.698G>T(p.Cys233Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 1,568,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

DHRS7
NM_016029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.919

Variant links:

Genes affected

DHRS7 (HGNC:21524): (dehydrogenase/reductase 7) This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) family, which has over 46,000 members. Members in this family are enzymes that metabolize many different compounds, such as steroid hormones, prostaglandins, retinoids, lipids and xenobiotics. [provided by RefSeq, Apr 2016]

DHRS7 links:

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCNX4 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 rank	MANE	Protein	UniProt
DHRS7	NM_016029.4 link	c.698G>T	p.Cys233Phe	missense_variant	Exon 5 of 7	ENST00000557185.6	NP_057113.1	Q9Y394-1
DHRS7	NM_001322280.2 link	c.548G>T	p.Cys183Phe	missense_variant	Exon 5 of 7		NP_001309209.1	Q9Y394-2
DHRS7	NM_001322282.2 link	c.458G>T	p.Cys153Phe	missense_variant	Exon 4 of 6		NP_001309211.1
DHRS7	NM_001322281.2 link	c.278G>T	p.Cys93Phe	missense_variant	Exon 5 of 7		NP_001309210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6 link	c.698G>T	p.Cys233Phe	missense_variant	Exon 5 of 7	1	NM_016029.4	ENSP00000451882.1		Q9Y394-1

Frequencies

GnomAD3 genomes

AF:

0.0000447

AC:

AN:

134314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000238

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000156

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000820

AC:

AN:

243846

Hom.:

AF XY:

0.00000757

AC XY:

AN XY:

132118

show subpopulations

Gnomad AFR exome

AF:

0.000129

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000558

AC:

AN:

1434036

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

713270

show subpopulations

Gnomad4 AFR exome

AF:

0.000188

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.11e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000447

AC:

AN:

134314

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

64496

show subpopulations

Gnomad4 AFR

AF:

0.000116

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000238

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000156

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.698G>T (p.C233F) alteration is located in exon 5 (coding exon 5) of the DHRS7 gene. This alteration results from a G to T substitution at nucleotide position 698, causing the cysteine (C) at amino acid position 233 to be replaced by a phenylalanine (F). 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;D;T;.

Eigen

Benign

0.069

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.70

.;T;.;T

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.4

M;M;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-9.0

D;D;.;D

REVEL

Uncertain

0.34

Sift

Benign

0.062

T;T;.;T

Sift4G

Uncertain

0.011

D;D;D;D

Polyphen

0.97

D;D;.;.

Vest4

0.46

MutPred

0.63

Loss of catalytic residue at C233 (P = 0.1339);Loss of catalytic residue at C233 (P = 0.1339);Loss of catalytic residue at C233 (P = 0.1339);.;

MVP

0.64

MPC

0.071

ClinPred

0.87

GERP RS

0.0035

Varity_R

0.43

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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