chr19-48813288-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016246.3(HSD17B14):​c.700G>A​(p.Glu234Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000689 in 1,450,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: HSD17B14 NM_016246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 3.61
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Glu234Lys	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>A	p.Glu234Lys	missense	Exon 9 of 9	ENSP00000263278.3	Q9BPX1
	HSD17B14	ENST00000867480.1		c.826G>A	p.Glu276Lys	missense	Exon 10 of 10	ENSP00000537539.1
	HSD17B14	ENST00000867481.1		c.709G>A	p.Glu237Lys	missense	Exon 9 of 9	ENSP00000537540.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000134 AC: 3 AN: 224346 AF XY: 0.0000165

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000935

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000689 AC: 10 AN: 1450740 Hom.: 0 Cov.: 32 AF XY: 0.00000555 AC XY: 4 AN XY: 720572

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

American (AMR) AF: 0.0000698 AC: 3 AN: 42966

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

East Asian (EAS) AF: 0.0000255 AC: 1 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: 0.000174 AC: 1 AN: 5748

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1106908

Other (OTH) AF: 0.0000167 AC: 1 AN: 59930

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0087	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Benign	0.077	T
Sift4G	Uncertain	0.043	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.71		Gain of ubiquitination at E234 (P = 0.0247)
MVP		0.50
MPC		0.39
ClinPred		0.94	D
GERP RS		4.5
Varity_R		0.76
gMVP		0.64
Mutation Taster		=76/24	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; COSMIC: COSV99622656; COSMIC: COSV99622656;