4-55346385-GCGGTGTGGCTC-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_024592.5(SRD5A3):c.50_60del(p.Ala17AspfsTer50) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A17A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRD5A3 NM_024592.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.64

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 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 23 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-55346385-GCGGTGTGGCTC-G is Pathogenic according to our data. Variant chr4-55346385-GCGGTGTGGCTC-G is described in ClinVar as [Pathogenic]. Clinvar id is 2446387.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A3	NM_024592.5	c.50_60del	p.Ala17AspfsTer50	frameshift_variant	1/5	ENST00000264228.9
SRD5A3	NM_001410732.1	c.50_60del	p.Ala17AspfsTer50	frameshift_variant	1/4
SRD5A3	XM_005265767.4	c.50_60del	p.Ala17AspfsTer50	frameshift_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A3	ENST00000264228.9	c.50_60del	p.Ala17AspfsTer50	frameshift_variant	1/5	1	NM_024592.5	P1
SRD5A3	ENST00000679836.1	c.50_60del	p.Ala17AspfsTer50	frameshift_variant	1/4
SRD5A3	ENST00000505210.1			upstream_gene_variant		3

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: criteria provided, single submitter

Submissions by phenotype

SRD5A3-congenital disorder of glycosylation Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Suma Genomics

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-56212552;