Genetic Variant NM_016029.4:c.499G>T (chr14-60153073-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_016029.4(DHRS7):c.499G>T(p.Val167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DHRS7
NM_016029.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29772764).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016029.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS7	NM_016029.4	MANE Select	c.499G>T	p.Val167Leu	missense	Exon 4 of 7	NP_057113.1	Q9Y394-1
DHRS7	NM_001322280.2		c.349G>T	p.Val117Leu	missense	Exon 4 of 7	NP_001309209.1	Q9Y394-2
DHRS7	NM_001322281.2		c.79G>T	p.Val27Leu	missense	Exon 4 of 7	NP_001309210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DHRS7	ENST00000557185.6	TSL:1 MANE Select	c.499G>T	p.Val167Leu	missense	Exon 4 of 7	ENSP00000451882.1	Q9Y394-1
DHRS7	ENST00000536410.6	TSL:1	c.349G>T	p.Val117Leu	missense	Exon 4 of 7	ENSP00000442993.2	Q9Y394-2
DHRS7	ENST00000554101.5	TSL:2	c.481G>T	p.Val161Leu	missense	Exon 4 of 6	ENSP00000450899.1	H0YJ66

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251390

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.018

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.50

PhyloP100

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.39

Sift

Benign

0.082

Sift4G

Benign

0.14

Polyphen

0.96

Vest4

0.26

MutPred

0.43

Loss of catalytic residue at V167 (P = 0.0685)

MVP

0.89

MPC

0.093

ClinPred

0.43

GERP RS

0.071

PromoterAI

-0.0040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.71

Mutation Taster

=83/17

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over