4-87374749-C-A

Variant names:

• chr4-87374749-C-A
• NM_016245.5:c.400G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016245.5(HSD17B11):​c.400G>T​(p.Asp134Tyr) 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: 33)
• Consequence: HSD17B11 NM_016245.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.93

Genes affected

HSD17B11 (HGNC:22960): (hydroxysteroid 17-beta dehydrogenase 11) Short-chain alcohol dehydrogenases, such as HSD17B11, metabolize secondary alcohols and ketones (Brereton et al., 2001 [PubMed 11165019]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B11	NM_016245.5	c.400G>T	p.Asp134Tyr	missense_variant	Exon 3 of 7	ENST00000358290.9	NP_057329.3
HSD17B11	XM_011532021.2	c.400G>T	p.Asp134Tyr	missense_variant	Exon 3 of 4		XP_011530323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B11	ENST00000358290.9	c.400G>T	p.Asp134Tyr	missense_variant	Exon 3 of 7	1	NM_016245.5	ENSP00000351035.4
HSD17B11	ENST00000507286.1	c.319-1934G>T		intron_variant	Intron 2 of 5	5		ENSP00000423775.1
HSD17B11	ENST00000508413.1	n.*73G>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.400G>T (p.D134Y) alteration is located in exon 3 (coding exon 3) of the HSD17B11 gene. This alteration results from a G to T substitution at nucleotide position 400, causing the aspartic acid (D) at amino acid position 134 to be replaced by a tyrosine (Y). 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	0.79
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.63	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-8.7	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.64
MutPred		0.56		Loss of disorder (P = 0.0432);
MVP		0.95
MPC		1.1
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-88295901;