chr14-60153028-G-C

Position:

• chr14-60153028-G-C

Variant summary

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

The NM_016029.4(DHRS7):​c.544C>G​(p.Gln182Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHRS7 NM_016029.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.14

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]

DHRS7 (HGNC:):

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=0.30646697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7	NM_016029.4	c.544C>G	p.Gln182Glu	missense_variant	4/7	ENST00000557185.6	NP_057113.1
DHRS7	NM_001322280.2	c.394C>G	p.Gln132Glu	missense_variant	4/7		NP_001309209.1
DHRS7	NM_001322281.2	c.124C>G	p.Gln42Glu	missense_variant	4/7		NP_001309210.1
DHRS7	NM_001322282.2	c.393+931C>G		intron_variant			NP_001309211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7	ENST00000557185.6	c.544C>G	p.Gln182Glu	missense_variant	4/7	1	NM_016029.4	ENSP00000451882.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.544C>G (p.Q182E) alteration is located in exon 4 (coding exon 4) of the DHRS7 gene. This alteration results from a C to G substitution at nucleotide position 544, causing the glutamine (Q) at amino acid position 182 to be replaced by a glutamic acid (E). 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	0.086
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.16	T;T;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	.;D;.;D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N;N;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.83	N;N;.;N
REVEL	Benign	0.22
Sift	Benign	0.35	T;T;.;T
Sift4G	Benign	0.85	T;T;T;T
Polyphen		0.046	B;B;.;.
Vest4		0.24
MutPred		0.72		Gain of ubiquitination at K184 (P = 0.0443);Gain of ubiquitination at K184 (P = 0.0443);Gain of ubiquitination at K184 (P = 0.0443);.;
MVP		0.97
MPC		0.050
ClinPred		0.17	T
GERP RS		4.5
Varity_R		0.13
gMVP		0.55

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: rs1896579445; hg19: chr14-60619746;