Genetic Variant SDR42E1:c.*1268A>G (chr16-81997843-T-C) – 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.*1268A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,180 control chromosomes in the GnomAD database, including 7,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7823 hom., cov: 32)

Exomes 𝑓: 0.33 ( 0 hom. )

Consequence

SDR42E1
NM_145168.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.311

Publications

17 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SDR42E1	NM_145168.3 link	c.*1268A>G	3_prime_UTR_variant	Exon 3 of 3	ENST00000328945.7	NP_660151.2
SDR42E1	XM_005256257.5 link	c.*1268A>G	3_prime_UTR_variant	Exon 4 of 4		XP_005256314.1
SDR42E1	XM_011523471.4 link	c.*1268A>G	3_prime_UTR_variant	Exon 3 of 3		XP_011521773.1
SDR42E1	XM_047434925.1 link	c.*1268A>G	3_prime_UTR_variant	Exon 3 of 3		XP_047290881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDR42E1	ENST00000328945.7 link	c.*1268A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_145168.3	ENSP00000332407.4

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43314

AN:

152056

Hom.:

7816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.301

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.285

AC:

43320

AN:

152174

Hom.:

7823

Cov.:

AF XY:

0.289

AC XY:

21477

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0724

AC:

3006

AN:

41542

American (AMR)

AF:

0.285

AC:

4364

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1178

AN:

3470

East Asian (EAS)

AF:

0.102

AC:

530

AN:

5184

South Asian (SAS)

AF:

0.326

AC:

1573

AN:

4822

European-Finnish (FIN)

AF:

0.431

AC:

4561

AN:

10572

Middle Eastern (MID)

AF:

0.284

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.398

AC:

27063

AN:

67976

Other (OTH)

AF:

0.301

AC:

634

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1462

2925

4387

5850

7312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.332

Hom.:

18490

Bravo

AF:

0.262

Asia WGS

AF:

0.230

AC:

803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

(source)

DANN

Benign

0.76

PhyloP100

-0.31

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over