4-55346331-C-G

Variant names:

• chr4-55346331-C-G
• rs771229701
• NM_024592.5:c.-6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024592.5(SRD5A3):​c.-6C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000777 in 1,286,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SRD5A3 NM_024592.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 0 publications found

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]

SRD5A3 Gene-Disease associations (from GenCC):

• SRD5A3-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P

ENSG00000288695 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024592.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A3	NM_024592.5	MANE Select	c.-6C>G		5_prime_UTR	Exon 1 of 5	NP_078868.1	Q9H8P0
	SRD5A3	NM_001410732.1		c.-6C>G		5_prime_UTR	Exon 1 of 4	NP_001397661.1	A0A7P0TBH6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A3	ENST00000264228.9	TSL:1 MANE Select	c.-6C>G		5_prime_UTR	Exon 1 of 5	ENSP00000264228.4	Q9H8P0
	ENSG00000288695	ENST00000679707.1		c.-6C>G		5_prime_UTR	Exon 1 of 6	ENSP00000505713.1	A0A7P0T9P9
	SRD5A3	ENST00000918496.1		c.-6C>G		5_prime_UTR	Exon 1 of 5	ENSP00000588555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.77e-7 AC: 1 AN: 1286990 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 631658

African (AFR) AF: 0.00 AC: 0 AN: 25668

American (AMR) AF: 0.00 AC: 0 AN: 17530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20600

East Asian (EAS) AF: 0.00 AC: 0 AN: 28102

South Asian (SAS) AF: 0.00 AC: 0 AN: 63894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3958

European-Non Finnish (NFE) AF: 9.70e-7 AC: 1 AN: 1031164

Other (OTH) AF: 0.00 AC: 0 AN: 52770

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		-0.080
PromoterAI		-0.024	Neutral

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

Other links and lift over

dbSNP: rs771229701; hg19: chr4-56212498;