chr3-58317208-C-T

Variant names:

• chr3-58317208-C-T
• rs73081554
• NM_001348712.2:c.-175+215C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348712.2(HTD2):​c.-175+215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 152,200 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.043 (191 hom., cov: 32)
• Consequence: HTD2 NM_001348712.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 33 publications found

Genes affected

HTD2 (HGNC:53111): (hydroxyacyl-thioester dehydratase type 2) This gene encodes a protein that localizes to the mitochondria and can function as a 3-hydroxyacyl thioester dehydratase. This gene is located just downstream of the gene for ribonuclease P/MRP subunit p14 (RPP14) in a genomic context that is conserved among animals. The upstream RPP14 gene is thought to be co-transcribed with this gene, and bicistronic transcripts may include open reading frames for both proteins. [provided by RefSeq, May 2017]

RPP14 (HGNC:30327): (ribonuclease P/MRP subunit p14) This gene encodes a subunit of ribonuclease P and has 3' to 5' exoribonuclease activity. Transcripts for this gene are bicistronic and include a conserved downstream open reading frame for the hydroxyacyl-thioester dehydratase type 2 (HTD2) gene. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTD2	NM_001348712.2	c.-175+215C>T		intron_variant	Intron 4 of 4	ENST00000461393.7	NP_001335641.1
RPP14	NM_007042.6	c.318+215C>T		intron_variant	Intron 5 of 5	ENST00000295959.10	NP_008973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTD2	ENST00000461393.7	c.-175+215C>T		intron_variant	Intron 4 of 4	1	NM_001348712.2	ENSP00000484277.1
RPP14	ENST00000295959.10	c.318+215C>T		intron_variant	Intron 5 of 5	1	NM_007042.6	ENSP00000295959.5

Frequencies

GnomAD3 genomes AF: 0.0432 AC: 6565 AN: 152082 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0431 AC: 6566 AN: 152200 Hom.: 191 Cov.: 32 AF XY: 0.0422 AC XY: 3140 AN XY: 74386

African (AFR) AF: 0.0120 AC: 499 AN: 41542

American (AMR) AF: 0.0244 AC: 373 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4820

European-Finnish (FIN) AF: 0.0584 AC: 616 AN: 10548

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4759 AN: 68020

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0575 Hom.: 593

Bravo AF: 0.0397

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.42
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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: rs73081554; hg19: chr3-58302935;