Variant 5-6633319-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001047.4(SRD5A1):c.-258G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 509,426 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.017 ( 35 hom., cov: 34)

Exomes 𝑓: 0.022 ( 121 hom. )

Consequence

SRD5A1
NM_001047.4 upstream_gene

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.761

Variant links:

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]

SRD5A1 links:

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]

NSUN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-6633319-G-A is Benign according to our data. Variant chr5-6633319-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 354075.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0172 (2625/152322) while in subpopulation NFE AF= 0.0272 (1852/68008). AF 95% confidence interval is 0.0262. There are 35 homozygotes in gnomad4. There are 1218 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SRD5A1	NM_001047.4 link	c.-258G>A	upstream_gene_variant	ENST00000274192.7	NP_001038.1	P18405
SRD5A1	NM_001324322.2 link	c.-232G>A	upstream_gene_variant		NP_001311251.1	P18405
SRD5A1	NM_001324323.2 link	c.-979G>A	upstream_gene_variant		NP_001311252.1	P18405B7Z4D8
SRD5A1	NR_136739.2 link	n.-121G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7 link	c.-258G>A		upstream_gene_variant		1	NM_001047.4	ENSP00000274192.5		P18405

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2625

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00516

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0250

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0272

Gnomad OTH

AF:

0.0181

GnomAD4 exome

AF:

0.0223

AC:

7971

AN:

357104

Hom.:

121

Cov.:

AF XY:

0.0226

AC XY:

4199

AN XY:

185634

show subpopulations

Gnomad4 AFR exome

AF:

0.00580

Gnomad4 AMR exome

AF:

0.00941

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0000431

Gnomad4 SAS exome

AF:

0.0252

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.0266

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0172

AC:

2625

AN:

152322

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1218

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00514

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.0144

Gnomad4 NFE

AF:

0.0272

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0207

Hom.:

Bravo

AF:

0.0165

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Intellectual Disability, Recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 11, 2018

GeneDx

Significance: Likely 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

-0.77

CADD

Benign

7.6

DANN

Benign

0.94

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over