NM_000197.2:c.489+7G>C

Variant names:

• chr9-96249744-C-G
• rs750302966
• NM_000197.2:c.489+7G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000197.2(HSD17B3):​c.489+7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD17B3 NM_000197.2 splice_region, intron
• Scores: Splicing: ADA: 0.00007134
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.307
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-96249744-C-G is Benign according to our data. Variant chr9-96249744-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2859767.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.489+7G>C		splice_region intron	N/A	NP_000188.1	P37058-1
	HSD17B3-AS1	NR_146524.1		n.422C>G		non_coding_transcript_exon	Exon 3 of 3
	SLC35D2-HSD17B3	NR_182427.1		n.3256+7G>C		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.489+7G>C		splice_region intron	N/A	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.489+7G>C		splice_region intron	N/A	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*2165+7G>C		splice_region intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.72
PhyloP100		-0.31

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000071
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.040		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: rs750302966; hg19: chr9-99012026;