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GeneBe

5-6651908-G-A

Variant summary

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

The NM_001047.4(SRD5A1):c.360G>A(p.Ala120=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000282 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

SRD5A1
NM_001047.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.02
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-6651908-G-A is Benign according to our data. Variant chr5-6651908-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 743374.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-6.02 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRD5A1NM_001047.4 linkuse as main transcriptc.360G>A p.Ala120= synonymous_variant 2/5 ENST00000274192.7
SRD5A1NM_001324323.2 linkuse as main transcriptc.141G>A p.Ala47= synonymous_variant 3/6
SRD5A1NM_001324322.2 linkuse as main transcriptc.320-4170G>A intron_variant
SRD5A1NR_136739.2 linkuse as main transcriptn.497G>A non_coding_transcript_exon_variant 2/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRD5A1ENST00000274192.7 linkuse as main transcriptc.360G>A p.Ala120= synonymous_variant 2/51 NM_001047.4 P1
SRD5A1ENST00000504286.2 linkuse as main transcriptc.360G>A p.Ala120= synonymous_variant, NMD_transcript_variant 2/62
SRD5A1ENST00000510531.6 linkuse as main transcriptc.*481G>A 3_prime_UTR_variant, NMD_transcript_variant 3/62
SRD5A1ENST00000513117.1 linkuse as main transcriptc.294-4170G>A intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000138
AC:
21
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000159
AC:
40
AN:
251268
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000868
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000264
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000297
AC:
434
AN:
1461630
Hom.:
0
Cov.:
32
AF XY:
0.000272
AC XY:
198
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.000370
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000138
AC:
21
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000153
Hom.:
0
Bravo
AF:
0.000181
EpiCase
AF:
0.000327
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.065
Dann
Benign
0.71

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

LitVar

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

Other links and lift over

dbSNP: rs142854865; hg19: chr5-6652021; COSMIC: COSV57013091; API