chr5-6651857-A-T

Variant names:

• chr5-6651857-A-T
• NM_001047.4:c.309A>T
• SRD5A1 p.Pro103Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001047.4(SRD5A1):​c.309A>T​(p.Pro103Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SRD5A1 NM_001047.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.96 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	NM_001047.4	MANE Select	c.309A>T	p.Pro103Pro	synonymous	Exon 2 of 5	NP_001038.1	P18405
	SRD5A1	NM_001324323.2		c.90A>T	p.Pro30Pro	synonymous	Exon 3 of 6	NP_001311252.1
	SRD5A1	NM_001324322.2		c.320-4221A>T		intron	N/A	NP_001311251.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A1	ENST00000274192.7	TSL:1 MANE Select	c.309A>T	p.Pro103Pro	synonymous	Exon 2 of 5	ENSP00000274192.5	P18405
	SRD5A1	ENST00000854432.1		c.309A>T	p.Pro103Pro	synonymous	Exon 2 of 6	ENSP00000524491.1
	SRD5A1	ENST00000854431.1		c.309A>T	p.Pro103Pro	synonymous	Exon 2 of 5	ENSP00000524490.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456768 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 724146

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44434

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4918

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109060

Other (OTH) AF: 0.00 AC: 0 AN: 60136

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-6651970;