Variant 13-51790085-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001377932.1(DHRS12):c.-11A>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000629 in 1,431,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

DHRS12
NM_001377932.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

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]

DHRS12 links:

ENSG00000285444 (HGNC:):

ENSG00000285444 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.906

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS12	NM_001377533.1 link	c.227A>T	p.Asn76Ile	missense_variant	4/9	ENST00000444610.8	NP_001364462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DHRS12	ENST00000444610.8 link	c.227A>T	p.Asn76Ile	missense_variant	4/9	1	NM_001377533.1	ENSP00000411565.3	A0PJE2-4A0A8C8L8Z5
ENSG00000285444	ENST00000642706.1 link	n.*374A>T		non_coding_transcript_exon_variant	7/11			ENSP00000495561.1	A0A2R8Y6I0
ENSG00000285444	ENST00000642706.1 link	n.*374A>T		3_prime_UTR_variant	7/11			ENSP00000495561.1	A0A2R8Y6I0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000136

AC:

AN:

220154

Hom.:

AF XY:

0.0000167

AC XY:

AN XY:

119658

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000392

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000629

AC:

AN:

1431408

Hom.:

Cov.:

AF XY:

0.00000843

AC XY:

AN XY:

711910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000556

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000634

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2022

The c.227A>T (p.N76I) alteration is located in exon 4 (coding exon 3) of the DHRS12 gene. This alteration results from a A to T substitution at nucleotide position 227, causing the asparagine (N) at amino acid position 76 to be replaced by an isoleucine (I). 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

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.68

D;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

3.9

H;.;.

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-8.3

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.93

MVP

0.68

MPC

0.74

ClinPred

1.0

GERP RS

2.1

Varity_R

0.81

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.30

Position offset: -6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over