19-48813288-C-G

Variant names:

• chr19-48813288-C-G
• rs1400589983
• NM_016246.3:c.700G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016246.3(HSD17B14):​c.700G>C​(p.Glu234Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E234K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HSD17B14 NM_016246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

Genes affected

HSD17B14 (HGNC:23238): (hydroxysteroid 17-beta dehydrogenase 14) 17-beta-hydroxysteroid dehydrogenases, such as HSD17B14, are primarily involved in metabolism of steroids at the C17 position and also of other substrates, such as fatty acids, prostaglandins, and xenobiotics (Lukacik et al., 2007 [PubMed 17067289]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34535497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016246.3. 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
	HSD17B14	NM_016246.3	MANE Select	c.700G>C	p.Glu234Gln	missense	Exon 9 of 9	NP_057330.2	Q9BPX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B14	ENST00000263278.9	TSL:1 MANE Select	c.700G>C	p.Glu234Gln	missense	Exon 9 of 9	ENSP00000263278.3	Q9BPX1
	HSD17B14	ENST00000867480.1		c.826G>C	p.Glu276Gln	missense	Exon 10 of 10	ENSP00000537539.1
	HSD17B14	ENST00000867481.1		c.709G>C	p.Glu237Gln	missense	Exon 9 of 9	ENSP00000537540.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450740 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 720572

African (AFR) AF: 0.00 AC: 0 AN: 33298

American (AMR) AF: 0.00 AC: 0 AN: 42966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25796

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 84444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106908

Other (OTH) AF: 0.00 AC: 0 AN: 59930

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0023	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.22
Sift	Benign	0.082	T
Sift4G	Benign	0.10	T
Polyphen		1.0	D
Vest4		0.18
MutPred		0.67		Loss of sheet (P = 0.1158)
MVP		0.47
MPC		0.46
ClinPred		0.91	D
GERP RS		4.5
Varity_R		0.69
gMVP		0.62
Mutation Taster		=73/27	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

dbSNP: rs1400589983; hg19: chr19-49316545;