4-55364177-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_024592.5(SRD5A3):​c.468C>T​(p.Val156Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SRD5A3
NM_024592.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.24
Variant links:
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-AS1 (HGNC:44138): (SRD5A3 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
Variant 4-55364177-C-T is Benign according to our data. Variant chr4-55364177-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3642602.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.24 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRD5A3NM_024592.5 linkc.468C>T p.Val156Val synonymous_variant Exon 3 of 5 ENST00000264228.9 NP_078868.1 Q9H8P0
SRD5A3NM_001410732.1 linkc.468C>T p.Val156Val synonymous_variant Exon 3 of 4 NP_001397661.1
SRD5A3XM_017008601.2 linkc.333C>T p.Val111Val synonymous_variant Exon 3 of 5 XP_016864090.1
SRD5A3XM_005265767.4 linkc.364+4689C>T intron_variant Intron 2 of 2 XP_005265824.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRD5A3ENST00000264228.9 linkc.468C>T p.Val156Val synonymous_variant Exon 3 of 5 1 NM_024592.5 ENSP00000264228.4 Q9H8P0
ENSG00000288695ENST00000679707.1 linkc.468C>T p.Val156Val synonymous_variant Exon 3 of 6 ENSP00000505713.1 A0A7P0T9P9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

SRD5A3-congenital disorder of glycosylation Benign:1
May 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.63
DANN
Benign
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-56230344; API