dbSNP rs6564956: SDR42E1:p.Ser10Thr (chr16-82000830-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145168.3(SDR42E1):c.29G>C(p.Ser10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,612,950 control chromosomes in the GnomAD database, including 5,071 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 2577 hom., cov: 32)

Exomes 𝑓: 0.020 ( 2494 hom. )

Consequence

SDR42E1
NM_145168.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.528

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0076619387).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDR42E1	NM_145168.3 link	c.29G>C	p.Ser10Thr	missense_variant	Exon 2 of 3	ENST00000328945.7	NP_660151.2	Q8WUS8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDR42E1	ENST00000328945.7 link	c.29G>C	p.Ser10Thr	missense_variant	Exon 2 of 3	1	NM_145168.3	ENSP00000332407.4	Q8WUS8
SDR42E1	ENST00000532128.5 link	c.-98G>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 4	5		ENSP00000434529.1	E9PQ06
SDR42E1	ENST00000534209.1 link	n.362G>C		non_coding_transcript_exon_variant	Exon 3 of 4	2
SDR42E1	ENST00000532128.5 link	c.-98G>C		5_prime_UTR_variant	Exon 2 of 4	5		ENSP00000434529.1	E9PQ06

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16107

AN:

152112

Hom.:

2558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.0429

Gnomad SAS

AF:

0.0728

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.0737

GnomAD2 exomes

AF:

0.0385

AC:

9574

AN:

248908

AF XY:

0.0341

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.0229

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0391

Gnomad FIN exome

AF:

0.000698

Gnomad NFE exome

AF:

0.00671

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0195

AC:

28489

AN:

1460720

Hom.:

2494

Cov.:

AF XY:

0.0196

AC XY:

14243

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.349

AC:

11590

AN:

33184

American (AMR)

AF:

0.0262

AC:

1171

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

280

AN:

26116

East Asian (EAS)

AF:

0.0228

AC:

903

AN:

39658

South Asian (SAS)

AF:

0.0568

AC:

4887

AN:

85988

European-Finnish (FIN)

AF:

0.000712

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.0423

AC:

243

AN:

5742

European-Non Finnish (NFE)

AF:

0.00639

AC:

7102

AN:

1111738

Other (OTH)

AF:

0.0377

AC:

2275

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

1082

2164

3246

4328

5410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.106

AC:

16165

AN:

152230

Hom.:

2577

Cov.:

AF XY:

0.104

AC XY:

7723

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.343

AC:

14231

AN:

41472

American (AMR)

AF:

0.0458

AC:

701

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.0419

AC:

217

AN:

5182

South Asian (SAS)

AF:

0.0729

AC:

352

AN:

4830

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00651

AC:

443

AN:

68036

Other (OTH)

AF:

0.0753

AC:

159

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

585

1169

1754

2338

2923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0144

Hom.:

124

Bravo

AF:

0.118

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.325

AC:

1212

ESP6500EA

AF:

0.00829

AC:

ExAC

AF:

0.0450

AC:

5438

Asia WGS

AF:

0.106

AC:

368

AN:

3478

EpiCase

AF:

0.00824

EpiControl

AF:

0.00830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.1

(source)

DANN

Benign

0.095

DEOGEN2

Benign

0.00040

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.039

MetaRNN

Benign

0.0077

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.96

PhyloP100

0.53

PrimateAI

Benign

0.36

PROVEAN

Benign

0.42

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.025

MPC

0.010

ClinPred

0.00014

GERP RS

2.5

Varity_R

0.056

gMVP

0.42

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over