NM_001047.4:c.110T>G

Variant names:

• chr5-6633686-T-G
• NM_001047.4:c.110T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001047.4(SRD5A1):​c.110T>G​(p.Val37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SRD5A1 NM_001047.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.998

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08128068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A1	NM_001047.4	c.110T>G	p.Val37Gly	missense_variant	Exon 1 of 5	ENST00000274192.7	NP_001038.1
SRD5A1	NM_001324322.2	c.136T>G	p.Cys46Gly	missense_variant	Exon 1 of 4		NP_001311251.1
SRD5A1	NM_001324323.2	c.-612T>G		5_prime_UTR_variant	Exon 1 of 6		NP_001311252.1
SRD5A1	NR_136739.2	n.247T>G		non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A1	ENST00000274192.7	c.110T>G	p.Val37Gly	missense_variant	Exon 1 of 5	1	NM_001047.4	ENSP00000274192.5
SRD5A1	ENST00000504286.1	n.231T>G		non_coding_transcript_exon_variant	Exon 1 of 3	2		ENSP00000518753.1
SRD5A1	ENST00000510531.5	n.110T>G		non_coding_transcript_exon_variant	Exon 1 of 6	2		ENSP00000425330.1
SRD5A1	ENST00000513117.1	n.110T>G		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000421342.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434746 Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1 AN XY: 713280

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	18
DANN	Benign	0.43
DEOGEN2	Benign	0.094	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.63	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.037
Sift	Benign	0.36	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.50		Loss of stability (P = 0.0103);
MVP		0.10
MPC		0.67
ClinPred		0.11	T
GERP RS		0.81
Varity_R		0.032
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 0

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-6633799;