rs8058588

Positions:

• chr16-22166889-C-T

Variant summary

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

The NM_001394319.2(SDR42E2):​c.241-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 650,742 control chromosomes in the GnomAD database, including 355 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 0.032 (255 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (100 hom.)
• Consequence: SDR42E2 NM_001394319.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

Genes affected

SDR42E2 (HGNC:35414): (short chain dehydrogenase/reductase family 42E, member 2) 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. [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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDR42E2	NM_001394319.2	c.241-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000602312.3	NP_001381248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDR42E2	ENST00000602312.3	c.241-15C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001394319.2	ENSP00000473474	P1
SDR42E2	ENST00000686682.1	c.853-15C>T		splice_polypyrimidine_tract_variant, intron_variant				ENSP00000509391
SDR42E2	ENST00000684942.1	c.853-15C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant				ENSP00000508835
SDR42E2	ENST00000687571.1	c.853-15C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant				ENSP00000509796

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4873 AN: 152070 Hom.: 254 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.00729 AC: 867 AN: 118868 Hom.: 42 AF XY: 0.00552 AC XY: 358 AN XY: 64864

Gnomad AFR exome AF: 0.108

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.000437

Gnomad EAS exome AF: 0.00280

Gnomad SAS exome AF: 0.000403

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000473

Gnomad OTH exome AF: 0.00518

GnomAD4 exome AF: 0.00474 AC: 2364 AN: 498554 Hom.: 100 Cov.: 0 AF XY: 0.00382 AC XY: 1018 AN XY: 266602

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.00632

Gnomad4 ASJ exome AF: 0.000777

Gnomad4 EAS exome AF: 0.00174

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000345

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.0322 AC: 4894 AN: 152188 Hom.: 255 Cov.: 32 AF XY: 0.0318 AC XY: 2363 AN XY: 74400

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.00716 Hom.: 40

Bravo AF: 0.0379

Asia WGS AF: 0.0290 AC: 102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.62

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: rs8058588; hg19: chr16-22178210;