5-6633334-C-T

Variant names:

• chr5-6633334-C-T
• rs8192125
• NM_001047.4:c.-243C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001047.4(SRD5A1):​c.-243C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 516,634 control chromosomes in the GnomAD database, including 14,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3137 hom., cov: 35)
  • Exomes 𝑓: 0.24 (11227 hom.)
• Consequence: SRD5A1 NM_001047.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.751

Genes affected

SRD5A1 (HGNC:11284): (steroid 5 alpha-reductase 1) Steroid 5-alpha-reductase (EC 1.3.99.5) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT). Also see SRD5A2 (MIM 607306).[supplied by OMIM, Mar 2008]

NSUN2 (HGNC:25994): (NOP2/Sun RNA methyltransferase 2) This gene encodes a methyltransferase that catalyzes the methylation of cytosine to 5-methylcytosine (m5C) at position 34 of intron-containing tRNA(Leu)(CAA) precursors. This modification is necessary to stabilize the anticodon-codon pairing and correctly translate the mRNA. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-6633334-C-T is Benign according to our data. Variant chr5-6633334-C-T is described in ClinVar as [Benign]. Clinvar id is 354077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.-243C>T		upstream_gene_variant		ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.-217C>T		upstream_gene_variant			NP_001311251.1
SRD5A1	NM_001324323.2	c.-964C>T		upstream_gene_variant			NP_001311252.1
SRD5A1	NR_136739.2	n.-106C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.-243C>T		upstream_gene_variant		1	NM_001047.4	ENSP00000274192.5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27944 AN: 152032 Hom.: 3138 Cov.: 35

Gnomad AFR AF: 0.0827

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.235 AC: 85663 AN: 364488 Hom.: 11227 Cov.: 5 AF XY: 0.238 AC XY: 45052 AN XY: 189218

Gnomad4 AFR exome AF: 0.0877

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.478

Gnomad4 SAS exome AF: 0.299

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.184 AC: 27940 AN: 152146 Hom.: 3137 Cov.: 35 AF XY: 0.188 AC XY: 13950 AN XY: 74376

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.204

Alfa AF: 0.189 Hom.: 370

Bravo AF: 0.171

Asia WGS AF: 0.314 AC: 1090 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual Disability, Recessive Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.94

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192125; hg19: chr5-6633447;