Variant 14-60150151-A-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_016029.4(DHRS7):c.670T>C(p.Tyr224His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000435 in 1,403,136 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

DHRS7
NM_016029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.81

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:

PCNX4 (HGNC:):

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/exons	MANE	Protein	UniProt
DHRS7	NM_016029.4 linkuse as main transcript	c.670T>C	p.Tyr224His	missense_variant	5/7	ENST00000557185.6	NP_057113.1	Q9Y394-1
DHRS7	NM_001322280.2 linkuse as main transcript	c.520T>C	p.Tyr174His	missense_variant	5/7		NP_001309209.1	Q9Y394-2
DHRS7	NM_001322282.2 linkuse as main transcript	c.430T>C	p.Tyr144His	missense_variant	4/6		NP_001309211.1
DHRS7	NM_001322281.2 linkuse as main transcript	c.250T>C	p.Tyr84His	missense_variant	5/7		NP_001309210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6 linkuse as main transcript	c.670T>C	p.Tyr224His	missense_variant	5/7	1	NM_016029.4	ENSP00000451882.1		Q9Y394-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000379

AC:

AN:

237414

Hom.:

AF XY:

0.0000388

AC XY:

AN XY:

128896

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:

0.0000822

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000435

AC:

AN:

1403136

Hom.:

Cov.:

AF XY:

0.0000501

AC XY:

AN XY:

698938

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:

0.0000550

Gnomad4 OTH exome

AF:

0.0000349

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Jul 22, 2024

The c.670T>C (p.Y224H) alteration is located in exon 5 (coding exon 5) of the DHRS7 gene. This alteration results from a T to C substitution at nucleotide position 670, causing the tyrosine (Y) at amino acid position 224 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

.;T;.;T

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.45

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.8

M;M;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

N;N;.;N

REVEL

Benign

0.18

Sift

Benign

0.20

T;T;.;T

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.32

B;B;.;.

Vest4

0.56

MutPred

0.45

Loss of stability (P = 0.126);Loss of stability (P = 0.126);Loss of stability (P = 0.126);.;

MVP

0.44

MPC

0.062

ClinPred

0.33

GERP RS

6.0

Varity_R

0.093

gMVP

0.59

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