12-56774051-G-T

Variant names:

• chr12-56774051-G-T
• rs148211848
• NM_003725.4:c.199G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003725.4(HSD17B6):​c.199G>T​(p.Glu67*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD17B6 NM_003725.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 0 publications found

Genes affected

HSD17B6 (HGNC:23316): (hydroxysteroid 17-beta dehydrogenase 6) The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013]

ENSG00000309589 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003725.4. 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
	HSD17B6	NM_003725.4	MANE Select	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 5	NP_003716.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B6	ENST00000322165.1	TSL:1 MANE Select	c.199G>T	p.Glu67*	stop_gained	Exon 2 of 5	ENSP00000318631.1	O14756
	HSD17B6	ENST00000859675.1		c.199G>T	p.Glu67*	stop_gained	Exon 2 of 6	ENSP00000529734.1
	HSD17B6	ENST00000554150.5	TSL:5	c.199G>T	p.Glu67*	stop_gained	Exon 3 of 6	ENSP00000452273.1	O14756

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Benign	0.10
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.36	N
PhyloP100		0.21
Vest4		0.31
GERP RS		0.73
Mutation Taster		=135/65	disease causing (fs/PTC)

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: rs148211848; hg19: chr12-57167835;