NM_024592.5:c.*70C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024592.5(SRD5A3):c.*70C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,590,128 control chromosomes in the GnomAD database, including 68,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6254 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61955 hom. )

Consequence

SRD5A3
NM_024592.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0430

Publications

19 publications found

Variant links:

Genes affected

SRD5A3 (HGNC:25812): (steroid 5 alpha-reductase 3) The protein encoded by this gene belongs to the steroid 5-alpha reductase family, and polyprenol reductase subfamily. It is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type Iq. [provided by RefSeq, Mar 2011]

SRD5A3 links:

ENSG00000288695 (HGNC:):

ENSG00000288695 links:

SRD5A3-AS1 (HGNC:44138): (SRD5A3 antisense RNA 1)

SRD5A3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-55370161-C-T is Benign according to our data. Variant chr4-55370161-C-T is described in ClinVar as Benign. ClinVar VariationId is 349009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A3	NM_024592.5 link	c.*70C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000264228.9	NP_078868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A3	ENST00000264228.9 link	c.*70C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_024592.5	ENSP00000264228.4
ENSG00000288695	ENST00000679707.1 link	c.563-1513C>T		intron_variant	Intron 3 of 5			ENSP00000505713.1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42644

AN:

151922

Hom.:

6247

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.290

AC:

416747

AN:

1438088

Hom.:

61955

Cov.:

AF XY:

0.294

AC XY:

210794

AN XY:

716776

show subpopulations

African (AFR)

AF:

0.252

AC:

8337

AN:

33028

American (AMR)

AF:

0.232

AC:

10351

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

6354

AN:

26032

East Asian (EAS)

AF:

0.133

AC:

5276

AN:

39618

South Asian (SAS)

AF:

0.389

AC:

33220

AN:

85472

European-Finnish (FIN)

AF:

0.355

AC:

17003

AN:

47938

Middle Eastern (MID)

AF:

0.247

AC:

1017

AN:

4114

European-Non Finnish (NFE)

AF:

0.290

AC:

318582

AN:

1097522

Other (OTH)

AF:

0.278

AC:

16607

AN:

59692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

15566

31132

46698

62264

77830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10420

20840

31260

41680

52100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.281

AC:

42672

AN:

152040

Hom.:

6254

Cov.:

AF XY:

0.285

AC XY:

21186

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.254

AC:

10528

AN:

41462

American (AMR)

AF:

0.253

AC:

3864

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

860

AN:

3470

East Asian (EAS)

AF:

0.107

AC:

554

AN:

5184

South Asian (SAS)

AF:

0.400

AC:

1924

AN:

4814

European-Finnish (FIN)

AF:

0.377

AC:

3975

AN:

10556

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20078

AN:

67968

Other (OTH)

AF:

0.263

AC:

554

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1597

3193

4790

6386

7983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.281

Hom.:

2394

Bravo

AF:

0.261

Asia WGS

AF:

0.284

AC:

989

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

SRD5A3-congenital disorder of glycosylation

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.9

(source)

DANN

Benign

0.32

PhyloP100

0.043

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over