rs587776521

Positions:

• chr4-55359409-TCAA-TTGAGTAAGGC

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_024592.5(SRD5A3):​c.286_288delinsTGAGTAAGGC​(p.Gln96Ter) variant causes a stop gained, frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRD5A3 NM_024592.5 stop_gained, frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.83

Genes affected

SRD5A3 (HGNC:25812): (steroid 5 alpha-reductase 3) The protein encoded by this gene belongs to the steroid 5-alpha reductase family, and polyprenol reductase subfamily. It is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type Iq. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-55359410-CAA-TGAGTAAGGC is Pathogenic according to our data. Variant chr4-55359410-CAA-TGAGTAAGGC is described in ClinVar as [Pathogenic]. Clinvar id is 18404.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A3	NM_024592.5	c.286_288delinsTGAGTAAGGC	p.Gln96Ter	stop_gained, frameshift_variant	2/5	ENST00000264228.9
SRD5A3	NM_001410732.1	c.286_288delinsTGAGTAAGGC	p.Gln96Ter	stop_gained, frameshift_variant	2/4
SRD5A3	XM_005265767.4	c.286_288delinsTGAGTAAGGC	p.Gln96Ter	stop_gained, frameshift_variant	2/3
SRD5A3	XM_017008601.2	c.151_153delinsTGAGTAAGGC	p.Gln51Ter	stop_gained, frameshift_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A3	ENST00000264228.9	c.286_288delinsTGAGTAAGGC	p.Gln96Ter	stop_gained, frameshift_variant	2/5	1	NM_024592.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

SRD5A3-congenital disorder of glycosylation Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 23, 2010

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587776521; hg19: chr4-56225577;