rs150326995

Variant names:

• chr5-119496624-C-A
• NM_000414.4:c.950C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-119496624-C-A
• chr5-119496624-C-T

Variant summary

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

The NM_000414.4(HSD17B4):​c.950C>A​(p.Thr317Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HSD17B4 NM_000414.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

Genes affected

HSD17B4 (HGNC:5213): (hydroxysteroid 17-beta dehydrogenase 4) The protein encoded by this gene is a bifunctional enzyme that is involved in the peroxisomal beta-oxidation pathway for fatty acids. It also acts as a catalyst for the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids. Defects in this gene that affect the peroxisomal fatty acid beta-oxidation activity are a cause of D-bifunctional protein deficiency (DBPD). An apparent pseudogene of this gene is present on chromosome 8. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

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=0.07805461).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B4	NM_000414.4	c.950C>A	p.Thr317Lys	missense_variant	Exon 12 of 24	ENST00000510025.7	NP_000405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B4	ENST00000510025.7	c.950C>A	p.Thr317Lys	missense_variant	Exon 12 of 24	2	NM_000414.4	ENSP00000424940.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445804 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 720394

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.099	T;.;T;.;.;.;T;.;T;.;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.81	.;T;T;.;T;T;T;T;T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.078	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.8	L;.;L;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.52	N;N;.;.;N;.;.;.;N;N;.
REVEL	Benign	0.094
Sift	Benign	0.58	T;T;.;.;T;.;.;.;T;T;.
Sift4G	Benign	0.95	T;T;.;.;T;.;.;.;T;T;.
Polyphen		0.037	B;.;B;.;.;.;B;.;.;P;.
Vest4		0.16
MutPred		0.30		Gain of ubiquitination at T317 (P = 0.0075);.;Gain of ubiquitination at T317 (P = 0.0075);.;.;Gain of ubiquitination at T317 (P = 0.0075);.;.;.;.;.;
MVP		0.80
MPC		0.10
ClinPred		0.21	T
GERP RS		3.6
Varity_R		0.038
gMVP		0.68

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: chr5-118832319;