chr4-87391031-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/20 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016245.5. 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
	HSD17B11	NM_016245.5	MANE Select	c.40C>G	p.Leu14Val	missense	Exon 1 of 7	NP_057329.3	Q8NBQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B11	ENST00000358290.9	TSL:1 MANE Select	c.40C>G	p.Leu14Val	missense	Exon 1 of 7	ENSP00000351035.4	Q8NBQ5
	HSD17B11	ENST00000854937.1		c.40C>G	p.Leu14Val	missense	Exon 1 of 7	ENSP00000524996.1
	HSD17B11	ENST00000854933.1		c.40C>G	p.Leu14Val	missense	Exon 1 of 7	ENSP00000524992.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-0.63	T
PhyloP100		1.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.28
Sift	Benign	0.59	T
Sift4G	Benign	0.54	T
Vest4		0.30
MutPred		0.46		Loss of stability (P = 0.4604)
MVP		0.63
MPC		0.99
ClinPred		0.29	T
GERP RS		6.0
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.33
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr4-88312183;