14-23955191-C-A

Variant names:

• chr14-23955191-C-A
• rs1367816310
• NM_021004.4:c.285C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021004.4(DHRS4):​c.285C>A​(p.Asp95Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHRS4 NM_021004.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 0 publications found

Genes affected

DHRS4 (HGNC:16985): (dehydrogenase/reductase 4) Enables identical protein binding activity; oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; and oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Involved in several processes, including cellular ketone metabolic process; positive regulation of reactive oxygen species metabolic process; and steroid metabolic process. Located in nucleus and peroxisomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
DHRS4	NM_021004.4	c.285C>A	p.Asp95Glu	missense_variant	Exon 2 of 8	ENST00000313250.10	NP_066284.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHRS4	ENST00000313250.10	c.285C>A	p.Asp95Glu	missense_variant	Exon 2 of 8	1	NM_021004.4	ENSP00000326219.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;D;.;.;.;.
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.65	D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.5	L;L;.;L;L;L;L
PhyloP100		0.57
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.040	D;T;T;D;D;D;D
Sift4G	Benign	0.080	T;T;T;T;T;T;T
Polyphen		0.84	P;P;P;P;.;D;D
Vest4		0.33
MutPred		0.49		Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);Gain of ubiquitination at K92 (P = 0.0756);
MVP		0.86
MPC		0.39
ClinPred		0.99	D
GERP RS		-0.047
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.65
gMVP		0.42
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs1367816310; hg19: chr14-24424400;