rs138228498

Variant names:

• chr1-162790823-C-A
• rs138228498
• NM_016371.4:c.23C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-162790823-C-A
• chr1-162790823-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016371.4(HSD17B7):​c.23C>A​(p.Thr8Asn) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T8S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 26)
• Consequence: HSD17B7 NM_016371.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

Genes affected

HSD17B7 (HGNC:5215): (hydroxysteroid 17-beta dehydrogenase 7) HSD17B7 encodes an enzyme that functions both as a 17-beta-hydroxysteroid dehydrogenase (EC 1.1.1.62) in the biosynthesis of sex steroids and as a 3-ketosteroid reductase (EC 1.1.1.270) in the biosynthesis of cholesterol (Marijanovic et al., 2003 [PubMed 12829805]).[supplied by OMIM, May 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B7	NM_016371.4	c.23C>A	p.Thr8Asn	missense_variant	Exon 1 of 9	ENST00000254521.8	NP_057455.1
HSD17B7	NM_001304512.2	c.23C>A	p.Thr8Asn	missense_variant	Exon 1 of 4		NP_001291441.1
HSD17B7	NM_001304513.2	c.23C>A	p.Thr8Asn	missense_variant	Exon 1 of 4		NP_001291442.1
HSD17B7	XR_007060779.1	n.122C>A		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B7	ENST00000254521.8	c.23C>A	p.Thr8Asn	missense_variant	Exon 1 of 9	1	NM_016371.4	ENSP00000254521.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.88	.;D;.
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.2	.;H;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.81
MutPred		0.90		Gain of MoRF binding (P = 0.1138);Gain of MoRF binding (P = 0.1138);Gain of MoRF binding (P = 0.1138);
MVP		0.99
MPC		1.5
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs138228498; hg19: chr1-162760613;