chr4-55370161-C-T

Variant names:

• chr4-55370161-C-T
• rs2538
• NM_024592.5:c.*70C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0430
• Publications: 19 publications found

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]

ENSG00000288695 (HGNC:):

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024592.5. 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
	SRD5A3	NM_024592.5	MANE Select	c.*70C>T		3_prime_UTR	Exon 5 of 5	NP_078868.1
	SRD5A3	NM_001410732.1		c.*70C>T		3_prime_UTR	Exon 4 of 4	NP_001397661.1
	SRD5A3-AS1	NR_037969.1		n.364-2998G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A3	ENST00000264228.9	TSL:1 MANE Select	c.*70C>T		3_prime_UTR	Exon 5 of 5	ENSP00000264228.4
	ENSG00000288695	ENST00000679707.1		c.563-1513C>T		intron	N/A	ENSP00000505713.1
	SRD5A3-AS1	ENST00000433175.6	TSL:1	n.269-2998G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42644 AN: 151922 Hom.: 6247 Cov.: 32

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.: 28 AF XY: 0.294 AC XY: 210794 AN XY: 716776

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

GnomAD4 genome AF: 0.281 AC: 42672 AN: 152040 Hom.: 6254 Cov.: 32 AF XY: 0.285 AC XY: 21186 AN XY: 74312

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: 75 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20078 AN: 67968

Other (OTH) AF: 0.263 AC: 554 AN: 2108

Alfa AF: 0.281 Hom.: 2394

Bravo AF: 0.261

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SRD5A3-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
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)

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: rs2538; hg19: chr4-56236328; COSMIC: COSV51711799; COSMIC: COSV51711799;