chr13-51773988-T-C

Position:

• chr13-51773988-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377533.1(DHRS12):​c.410A>G​(p.Asn137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DHRS12 NM_001377533.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.964

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06457558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS12	NM_001377533.1	c.410A>G	p.Asn137Ser	missense_variant	6/9	ENST00000444610.8	NP_001364462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS12	ENST00000444610.8	c.410A>G	p.Asn137Ser	missense_variant	6/9	1	NM_001377533.1	ENSP00000411565.3
ENSG00000285444	ENST00000642706.1	n.*557A>G		non_coding_transcript_exon_variant	9/11			ENSP00000495561.1
ENSG00000285444	ENST00000642706.1	n.*557A>G		3_prime_UTR_variant	9/11			ENSP00000495561.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251444 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135900

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 AF: 0.00000137 AC: 2 AN: 1461806 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Aug 21, 2023

The c.410A>G (p.N137S) alteration is located in exon 6 (coding exon 5) of the DHRS12 gene. This alteration results from a A to G substitution at nucleotide position 410, causing the asparagine (N) at amino acid position 137 to be replaced by a serine (S). 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	0.062
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.043
DANN	Benign	0.23
DEOGEN2	Benign	0.0022	T;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.065	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.49	N;N;N;.
REVEL	Benign	0.053
Sift	Benign	0.77	T;T;T;.
Sift4G	Benign	0.83	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.041
MutPred		0.45		Gain of catalytic residue at K182 (P = 0.0071);.;.;.;
MVP		0.18
MPC		0.13
ClinPred		0.043	T
GERP RS		-1.6
Varity_R		0.019
gMVP		0.062

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: rs1281987336; hg19: chr13-52348124;