19-48834344-C-A

Variant names:

• chr19-48834344-C-A
• rs1194600006
• NM_016246.3:c.142G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016246.3(HSD17B14):​c.142G>T​(p.Ala48Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A48T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HSD17B14 NM_016246.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1991888).

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.142G>T	p.Ala48Ser	missense	Exon 3 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.142G>T	p.Ala48Ser	missense	Exon 3 of 9	ENSP00000263278.3	Q9BPX1
	HSD17B14	ENST00000867480.1		c.142G>T	p.Ala48Ser	missense	Exon 3 of 10	ENSP00000537539.1
	HSD17B14	ENST00000867481.1		c.151G>T	p.Ala51Ser	missense	Exon 3 of 9	ENSP00000537540.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461248 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726976

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111634

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.30	T
Sift4G	Benign	0.52	T
Polyphen		0.0060	B
Vest4		0.37
MutPred		0.43		Gain of phosphorylation at A48 (P = 0.0485)
MVP		0.56
MPC		0.24
ClinPred		0.063	T
GERP RS		2.8
Varity_R		0.20
gMVP		0.46
Mutation Taster		=86/14	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: rs1194600006; hg19: chr19-49337601;