chrX-53431590-C-G

Variant names:

• chrX-53431590-C-G
• rs1255652783
• NM_004493.3:c.600G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_004493.3(HSD17B10):​c.600G>C​(p.Leu200Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,085,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes 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: 0.000010 (0 hom. 3 hem.)
• Consequence: HSD17B10 NM_004493.3 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36
• Publications: 1 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]

RIBC1 (HGNC:26537): (RIB43A domain with coiled-coils 1)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.068970144).
• BP7: Synonymous conserved (PhyloP=-1.36 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B10	NM_004493.3	MANE Select	c.600G>C	p.Leu200Leu	synonymous	Exon 6 of 6	NP_004484.1	A0A0S2Z410
	HSD17B10	NM_001037811.2		c.573G>C	p.Leu191Leu	synonymous	Exon 6 of 6	NP_001032900.1	Q99714-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B10	ENST00000168216.11	TSL:1 MANE Select	c.600G>C	p.Leu200Leu	synonymous	Exon 6 of 6	ENSP00000168216.6	Q99714-1
	HSD17B10	ENST00000375304.9	TSL:1	c.573G>C	p.Leu191Leu	synonymous	Exon 6 of 6	ENSP00000364453.5	Q99714-2
	HSD17B10	ENST00000375298.4	TSL:3	c.491G>C	p.Cys164Ser	missense	Exon 5 of 5	ENSP00000364447.4	Q5H928

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000615 AC: 1 AN: 162701 AF XY: 0.0000195

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000142

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000101 AC: 11 AN: 1085491 Hom.: 0 Cov.: 30 AF XY: 0.00000851 AC XY: 3 AN XY: 352461

African (AFR) AF: 0.0000763 AC: 2 AN: 26197

American (AMR) AF: 0.00 AC: 0 AN: 33951

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19185

East Asian (EAS) AF: 0.00 AC: 0 AN: 29894

South Asian (SAS) AF: 0.00 AC: 0 AN: 52672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40015

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.0000108 AC: 9 AN: 833794

Other (OTH) AF: 0.00 AC: 0 AN: 45667

GnomAD4 genome Cov.: 23

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	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0051	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	0.32
DANN	Benign	0.71
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.29	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.32	T
PhyloP100		-1.4
PROVEAN	Benign	2.8	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.38	T
Vest4		0.12
MutPred		0.58		Gain of disorder (P = 0.0075)
MVP		0.75
ClinPred		0.050	T
GERP RS		-9.3
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1255652783; hg19: chrX-53458538;