5-6651857-A-G

Variant names:

• chr5-6651857-A-G
• rs3822430
• NM_001047.4:c.309A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001047.4(SRD5A1):​c.309A>G​(p.Pro103Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,606,288 control chromosomes in the GnomAD database, including 106,157 homozygotes. 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: 𝑓 0.35 (9385 hom., cov: 32)
  • Exomes 𝑓: 0.36 (96772 hom.)
• Consequence: SRD5A1 NM_001047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 28 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001047.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	NM_001047.4	MANE Select	c.309A>G	p.Pro103Pro	synonymous	Exon 2 of 5	NP_001038.1
	SRD5A1	NM_001324323.2		c.90A>G	p.Pro30Pro	synonymous	Exon 3 of 6	NP_001311252.1
	SRD5A1	NR_136739.2		n.446A>G		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.309A>G	p.Pro103Pro	synonymous	Exon 2 of 5	ENSP00000274192.5
	SRD5A1	ENST00000504286.2	TSL:2	n.309A>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000518753.1
	SRD5A1	ENST00000510531.6	TSL:2	n.*430A>G		non_coding_transcript_exon	Exon 3 of 6	ENSP00000425330.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52741 AN: 151948 Hom.: 9373 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.329 AC: 82069 AN: 249338 AF XY: 0.327

Gnomad AFR exome AF: 0.333

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.461

Gnomad EAS exome AF: 0.170

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.359 AC: 521525 AN: 1454222 Hom.: 96772 Cov.: 34 AF XY: 0.355 AC XY: 256507 AN XY: 722868

African (AFR) AF: 0.342 AC: 11372 AN: 33298

American (AMR) AF: 0.336 AC: 14876 AN: 44308

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11975 AN: 26038

East Asian (EAS) AF: 0.163 AC: 6464 AN: 39594

South Asian (SAS) AF: 0.220 AC: 18830 AN: 85558

European-Finnish (FIN) AF: 0.315 AC: 16786 AN: 53312

Middle Eastern (MID) AF: 0.380 AC: 1865 AN: 4908

European-Non Finnish (NFE) AF: 0.378 AC: 418080 AN: 1107142

Other (OTH) AF: 0.354 AC: 21277 AN: 60064

GnomAD4 genome AF: 0.347 AC: 52793 AN: 152066 Hom.: 9385 Cov.: 32 AF XY: 0.341 AC XY: 25349 AN XY: 74340

African (AFR) AF: 0.336 AC: 13940 AN: 41470

American (AMR) AF: 0.355 AC: 5426 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1576 AN: 3470

East Asian (EAS) AF: 0.160 AC: 828 AN: 5176

South Asian (SAS) AF: 0.218 AC: 1048 AN: 4816

European-Finnish (FIN) AF: 0.307 AC: 3237 AN: 10550

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25404 AN: 67992

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.370 Hom.: 33034

Bravo AF: 0.354

Asia WGS AF: 0.190 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.17
DANN	Benign	0.62
PhyloP100		-2.0
Mutation Taster		=99/1	polymorphism (auto)

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: rs3822430; hg19: chr5-6651970; COSMIC: COSV57013381;