Variant 16-81999140-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_145168.3(SDR42E1):c.1153C>A(p.Leu385Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,916 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00092 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

SDR42E1
NM_145168.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694

Variant links:

Genes affected

SDR42E1 (HGNC:29834): (short chain dehydrogenase/reductase family 42E, member 1) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. Predicted to be involved in steroid biosynthetic process. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SDR42E1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04658267).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SDR42E1	NM_145168.3 linkuse as main transcript	c.1153C>A	p.Leu385Met	missense_variant	3/3	ENST00000328945.7
SDR42E1	XM_005256257.5 linkuse as main transcript	c.1153C>A	p.Leu385Met	missense_variant	4/4
SDR42E1	XM_011523471.4 linkuse as main transcript	c.1144C>A	p.Leu382Met	missense_variant	3/3
SDR42E1	XM_047434925.1 linkuse as main transcript	c.1144C>A	p.Leu382Met	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDR42E1	ENST00000328945.7 linkuse as main transcript	c.1153C>A	p.Leu385Met	missense_variant	3/3	1	NM_145168.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000742

AC:

185

AN:

249186

Hom.:

AF XY:

0.000725

AC XY:

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000493

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.00135

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.00146

AC:

2131

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

984

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000918

Gnomad4 NFE exome

AF:

0.00178

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152192

Hom.:

Cov.:

AF XY:

0.000888

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000290

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00108

AC:

ExAC

AF:

0.000712

AC:

EpiCase

AF:

0.00202

EpiControl

AF:

0.00148

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 19, 2021

The c.1153C>A (p.L385M) alteration is located in exon 3 (coding exon 2) of the SDR42E1 gene. This alteration results from a C to A substitution at nucleotide position 1153, causing the leucine (L) at amino acid position 385 to be replaced by a methionine (M). 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

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.46

M_CAP

Benign

0.075

MetaRNN

Benign

0.047

MetaSVM

Uncertain

-0.047

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.89

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.76

REVEL

Uncertain

0.37

Sift

Uncertain

0.014

Sift4G

Uncertain

0.034

Polyphen

0.97

Vest4

0.24

MVP

0.49

MPC

0.054

ClinPred

0.058

GERP RS

2.9

Varity_R

0.11

gMVP

0.55

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

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