NM_016029.4:c.499G>T

Variant names:

• chr14-60153073-C-A
• rs1468346332
• NM_016029.4:c.499G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 14/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.02

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29772764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7	NM_016029.4	c.499G>T	p.Val167Leu	missense_variant	Exon 4 of 7	ENST00000557185.6	NP_057113.1
DHRS7	NM_001322280.2	c.349G>T	p.Val117Leu	missense_variant	Exon 4 of 7		NP_001309209.1
DHRS7	NM_001322281.2	c.79G>T	p.Val27Leu	missense_variant	Exon 4 of 7		NP_001309210.1
DHRS7	NM_001322282.2	c.393+886G>T		intron_variant	Intron 3 of 5		NP_001309211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6	c.499G>T	p.Val167Leu	missense_variant	Exon 4 of 7	1	NM_016029.4	ENSP00000451882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251390 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135858

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 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 Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.499G>T (p.V167L) alteration is located in exon 4 (coding exon 4) of the DHRS7 gene. This alteration results from a G to T substitution at nucleotide position 499, causing the valine (V) at amino acid position 167 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	-0.080	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;T;T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.87	.;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.50	N;N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N;N;.;N
REVEL	Uncertain	0.39
Sift	Benign	0.082	T;T;.;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.96	D;D;.;.
Vest4		0.26
MutPred		0.43		Loss of catalytic residue at V167 (P = 0.0685);Loss of catalytic residue at V167 (P = 0.0685);Loss of catalytic residue at V167 (P = 0.0685);.;
MVP		0.89
MPC		0.093
ClinPred		0.43	T
GERP RS		0.071
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.069
gMVP		0.71

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

Other links and lift over

dbSNP: rs1468346332; hg19: chr14-60619791;