chr13-51777081-C-G

Position:

• chr13-51777081-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001377533.1(DHRS12):​c.342G>C​(p.Glu114Asp) 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. 13/21 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: DHRS12 NM_001377533.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.43

Genes affected

DHRS12 (HGNC:25832): (dehydrogenase/reductase 12) 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. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ENSG00000285444 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22071475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS12	NM_001377533.1	c.342G>C	p.Glu114Asp	missense_variant	5/9	ENST00000444610.8	NP_001364462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS12	ENST00000444610.8	c.342G>C	p.Glu114Asp	missense_variant	5/9	1	NM_001377533.1	ENSP00000411565.3
ENSG00000285444	ENST00000642706.1	n.*489G>C		non_coding_transcript_exon_variant	8/11			ENSP00000495561.1
ENSG00000285444	ENST00000642706.1	n.*489G>C		3_prime_UTR_variant	8/11			ENSP00000495561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 11, 2021

The c.342G>C (p.E114D) alteration is located in exon 5 (coding exon 4) of the DHRS12 gene. This alteration results from a G to C substitution at nucleotide position 342, causing the glutamic acid (E) at amino acid position 114 to be replaced by an aspartic acid (D). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	N;N;N;.
REVEL	Benign	0.058
Sift	Benign	0.057	T;T;T;.
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.026	B;B;D;.
Vest4		0.28
MutPred		0.50		Gain of catalytic residue at L158 (P = 0);.;.;.;
MVP		0.35
MPC		0.25
ClinPred		0.66	D
GERP RS		1.2
Varity_R		0.13
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-52351217;