4-87391031-G-C

Variant names:

• chr4-87391031-G-C
• NM_016245.5:c.40C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016245.5(HSD17B11):​c.40C>G​(p.Leu14Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD17B11 NM_016245.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.03

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14816457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B11	NM_016245.5	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 7	ENST00000358290.9	NP_057329.3
HSD17B11	XM_011532021.2	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 4		XP_011530323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B11	ENST00000358290.9	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 7	1	NM_016245.5	ENSP00000351035.4
HSD17B11	ENST00000507286.1	c.40C>G	p.Leu14Val	missense_variant	Exon 1 of 6	5		ENSP00000423775.1
HSD17B11	ENST00000508413.1	n.158C>G		non_coding_transcript_exon_variant	Exon 1 of 4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.40C>G (p.L14V) alteration is located in exon 1 (coding exon 1) of the HSD17B11 gene. This alteration results from a C to G substitution at nucleotide position 40, causing the leucine (L) at amino acid position 14 to be replaced by a valine (V). 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	Benign	0.13
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.60
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.49	.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.63	T
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.28
Sift	Benign	0.59	T;T
Sift4G	Benign	0.54	T;T
Vest4		0.30
MutPred		0.46		Loss of stability (P = 0.4604);Loss of stability (P = 0.4604);
MVP		0.63
MPC		0.99
ClinPred		0.29	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.33

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-88312183;