9-96249995-C-T

Variant names:

• chr9-96249995-C-T
• rs407179
• NM_000197.2:c.454-209G>A

Variant summary

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

The NM_000197.2(HSD17B3):​c.454-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,459,970 control chromosomes in the GnomAD database, including 52,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6628 hom., cov: 32)
  • Exomes 𝑓: 0.26 (46365 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.901
• Publications: 8 publications found

Genes affected

HSD17B3 (HGNC:5212): (hydroxysteroid 17-beta dehydrogenase 3) This isoform of 17 beta-hydroxysteroid dehydrogenase is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in male pseudohermaphroditism with gynecomastia. [provided by RefSeq, Jul 2008]

ENSG00000285269 (HGNC:):

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-96249995-C-T is Benign according to our data. Variant chr9-96249995-C-T is described in ClinVar as Benign. ClinVar VariationId is 1182347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.454-209G>A		intron	N/A	NP_000188.1
	HSD17B3-AS1	NR_146524.1		n.673C>T		non_coding_transcript_exon	Exon 3 of 3
	SLC35D2-HSD17B3	NR_182427.1		n.3221-209G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.454-209G>A		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.454-209G>A		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*2130-209G>A		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43112 AN: 151952 Hom.: 6619 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.259 AC: 338578 AN: 1307900 Hom.: 46365 Cov.: 31 AF XY: 0.255 AC XY: 162774 AN XY: 637162

African (AFR) AF: 0.396 AC: 11555 AN: 29180

American (AMR) AF: 0.163 AC: 4157 AN: 25442

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 5590 AN: 20314

East Asian (EAS) AF: 0.0211 AC: 739 AN: 35022

South Asian (SAS) AF: 0.145 AC: 9451 AN: 65024

European-Finnish (FIN) AF: 0.279 AC: 8727 AN: 31298

Middle Eastern (MID) AF: 0.335 AC: 1480 AN: 4420

European-Non Finnish (NFE) AF: 0.272 AC: 283274 AN: 1042684

Other (OTH) AF: 0.250 AC: 13605 AN: 54516

GnomAD4 genome AF: 0.284 AC: 43156 AN: 152070 Hom.: 6628 Cov.: 32 AF XY: 0.277 AC XY: 20569 AN XY: 74336

African (AFR) AF: 0.380 AC: 15738 AN: 41456

American (AMR) AF: 0.212 AC: 3247 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 935 AN: 3470

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5174

South Asian (SAS) AF: 0.136 AC: 655 AN: 4826

European-Finnish (FIN) AF: 0.286 AC: 3017 AN: 10566

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18483 AN: 67974

Other (OTH) AF: 0.272 AC: 574 AN: 2110

Alfa AF: 0.269 Hom.: 9746

Bravo AF: 0.283

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.54
PhyloP100		-0.90
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: rs407179; hg19: chr9-99012277;