chr4-87317105-A-G

Variant names:

• chr4-87317105-A-G
• NM_178135.5:c.437T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_178135.5(HSD17B13):​c.437T>C​(p.Leu146Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD17B13 NM_178135.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87
• Publications: 0 publications found

Genes affected

HSD17B13 (HGNC:18685): (hydroxysteroid 17-beta dehydrogenase 13) Predicted to enable oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and steroid dehydrogenase activity. Acts upstream of or within positive regulation of lipid biosynthetic process. Located in lipid droplet. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255723 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B13	NM_178135.5	c.437T>C	p.Leu146Pro	missense_variant	Exon 3 of 7	ENST00000328546.5	NP_835236.2
HSD17B13	NM_001136230.3	c.329T>C	p.Leu110Pro	missense_variant	Exon 2 of 6		NP_001129702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B13	ENST00000328546.5	c.437T>C	p.Leu146Pro	missense_variant	Exon 3 of 7	1	NM_178135.5	ENSP00000333300.4
HSD17B13	ENST00000302219.10	c.329T>C	p.Leu110Pro	missense_variant	Exon 2 of 6	1		ENSP00000305438.6
ENSG00000255723	ENST00000508163.1	n.*65T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.437T>C (p.L146P) alteration is located in exon 3 (coding exon 3) of the HSD17B13 gene. This alteration results from a T to C substitution at nucleotide position 437, causing the leucine (L) at amino acid position 146 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.64	.;D
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Pathogenic	3.6	.;H
PhyloP100		5.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Pathogenic	0.87
Sift	Uncertain	0.0080	D;T
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.64		.;Loss of stability (P = 0.0119);
MVP		0.99
MPC		0.67
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.89
gMVP		0.80
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr4-88238257;