rs6564956

Positions:

• chr16-82000830-C-G
• chr16-82000830-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (2577 hom., cov: 32)
  • Exomes 𝑓: 0.020 (2494 hom.)
• Consequence: SDR42E1 NM_145168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SDR42E1	NM_145168.3	c.29G>C	p.Ser10Thr	missense_variant	2/3	ENST00000328945.7	NP_660151.2
SDR42E1	XM_005256257.5	c.29G>C	p.Ser10Thr	missense_variant	3/4		XP_005256314.1
SDR42E1	XM_011523471.4	c.-98G>C		5_prime_UTR_variant	1/3		XP_011521773.1
SDR42E1	XM_047434925.1	c.-95G>C		5_prime_UTR_variant	1/3		XP_047290881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDR42E1	ENST00000328945.7	c.29G>C	p.Ser10Thr	missense_variant	2/3	1	NM_145168.3	ENSP00000332407	P1
SDR42E1	ENST00000532128.5	c.-98G>C		5_prime_UTR_variant	2/4	5		ENSP00000434529
SDR42E1	ENST00000534209.1	n.362G>C		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16107 AN: 152112 Hom.: 2558 Cov.: 32

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

GnomAD3 exomes AF: 0.0385 AC: 9574 AN: 248908 Hom.: 1042 AF XY: 0.0341 AC XY: 4604 AN XY: 135104

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 SAS exome AF: 0.0574

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.: 30 AF XY: 0.0196 AC XY: 14243 AN XY: 726704

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.0262

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.0568

Gnomad4 FIN exome AF: 0.000712

Gnomad4 NFE exome AF: 0.00639

Gnomad4 OTH exome AF: 0.0377

GnomAD4 genome AF: 0.106 AC: 16165 AN: 152230 Hom.: 2577 Cov.: 32 AF XY: 0.104 AC XY: 7723 AN XY: 74442

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.0458

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00651

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.0144 Hom.: 124

Bravo AF: 0.118

TwinsUK AF: 0.00782 AC: 29

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.325 AC: 1212

ESP6500EA AF: 0.00829 AC: 68

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	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.1
DANN	Benign	0.095
DEOGEN2	Benign	0.00040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.039	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.96	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.025
MPC		0.010
ClinPred		0.00014	T
GERP RS		2.5
Varity_R		0.056
gMVP		0.42

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: rs6564956; hg19: chr16-82034435; COSMIC: COSV100200652;