rs5939175

Positions:

• chrX-2408741-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_145177.3(DHRSX):​c.286+4C>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,606,450 control chromosomes in the GnomAD database, including 41,220 homozygotes. There are 168,329 hemizygotes in GnomAD. 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 0.30 (8481 hom., 21702 hem., cov: 31)
  • Exomes 𝑓: 0.20 (32739 hom. 146627 hem.)
• Consequence: DHRSX NM_145177.3 splice_donor_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

Genes affected

DHRSX (HGNC:18399): (dehydrogenase/reductase X-linked) Predicted to enable oxidoreductase activity. Involved in positive regulation of autophagy. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRSX	NM_145177.3	c.286+4C>G		splice_donor_region_variant, intron_variant		ENST00000334651.11	NP_660160.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRSX	ENST00000334651.11	c.286+4C>G		splice_donor_region_variant, intron_variant		1	NM_145177.3	ENSP00000334113	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44700 AN: 151328 Hom.: 8462 Cov.: 31 AF XY: 0.293 AC XY: 21649 AN XY: 73798

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.232 AC: 56918 AN: 245566 Hom.: 7854 AF XY: 0.230 AC XY: 30485 AN XY: 132554

Gnomad AFR exome AF: 0.540

Gnomad AMR exome AF: 0.195

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.281

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.199 AC: 289532 AN: 1455018 Hom.: 32739 Cov.: 34 AF XY: 0.203 AC XY: 146627 AN XY: 723470

Gnomad4 AFR exome AF: 0.548

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.177

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.296 AC: 44753 AN: 151432 Hom.: 8481 Cov.: 31 AF XY: 0.294 AC XY: 21702 AN XY: 73912

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.303

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.023
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.25		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5939175; hg19: chrX-2326782; COSMIC: COSV58131563;