1-162790823-C-A

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 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
• Publications: 1 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016371.4. 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
	HSD17B7	NM_016371.4	MANE Select	c.23C>A	p.Thr8Asn	missense	Exon 1 of 9	NP_057455.1	P56937-1
	HSD17B7	NM_001304512.2		c.23C>A	p.Thr8Asn	missense	Exon 1 of 4	NP_001291441.1
	HSD17B7	NM_001304513.2		c.23C>A	p.Thr8Asn	missense	Exon 1 of 4	NP_001291442.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B7	ENST00000254521.8	TSL:1 MANE Select	c.23C>A	p.Thr8Asn	missense	Exon 1 of 9	ENSP00000254521.3	P56937-1
	HSD17B7	ENST00000902168.1		c.23C>A	p.Thr8Asn	missense	Exon 1 of 9	ENSP00000572227.1
	HSD17B7	ENST00000963897.1		c.23C>A	p.Thr8Asn	missense	Exon 1 of 9	ENSP00000633956.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.2	H
PhyloP100		5.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.90		Gain of MoRF binding (P = 0.1138)
MVP		0.99
MPC		1.5
ClinPred		1.0	D
GERP RS		4.8
PromoterAI		-0.0097	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.85
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs138228498; hg19: chr1-162760613;