rs797045616

Variant names:

• chrX-53432108-G-A
• rs797045616
• NM_004493.3:c.366C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004493.3(HSD17B10):​c.366C>T​(p.Leu122Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,098,061 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: HSD17B10 NM_004493.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.548
• Publications: 0 publications found

Genes affected

HSD17B10 (HGNC:4800): (hydroxysteroid 17-beta dehydrogenase 10) This gene encodes 3-hydroxyacyl-CoA dehydrogenase type II, a member of the short-chain dehydrogenase/reductase superfamily. The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation. The protein has been implicated in the development of Alzheimer disease, and mutations in the gene are the cause of 17beta-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Aug 2014]

HSD17B10 Gene-Disease associations (from GenCC):

• HSD10 mitochondrial disease

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• HSD10 disease, infantile type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• HSD10 disease, neonatal type

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• syndromic X-linked intellectual disability type 10

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.548 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004493.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B10	NM_004493.3	MANE Select	c.366C>T	p.Leu122Leu	synonymous	Exon 4 of 6	NP_004484.1
	HSD17B10	NM_001037811.2		c.366C>T	p.Leu122Leu	synonymous	Exon 4 of 6	NP_001032900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B10	ENST00000168216.11	TSL:1 MANE Select	c.366C>T	p.Leu122Leu	synonymous	Exon 4 of 6	ENSP00000168216.6
	HSD17B10	ENST00000375304.9	TSL:1	c.366C>T	p.Leu122Leu	synonymous	Exon 4 of 6	ENSP00000364453.5
	HSD17B10	ENST00000684692.1		c.366C>T	p.Leu122Leu	synonymous	Exon 4 of 5	ENSP00000506792.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1098061 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363419

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30202

South Asian (SAS) AF: 0.00 AC: 0 AN: 54138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 842009

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		-0.55

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: rs797045616; hg19: chrX-53459056; COSMIC: COSV51447625; COSMIC: COSV51447625;