10-70144239-T-G

Variant names:

• chr10-70144239-T-G
• rs3763735
• NM_173555.4:c.1167-267A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173555.4(TYSND1):​c.1167-267A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: TYSND1 NM_173555.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 6 publications found

Genes affected

TYSND1 (HGNC:28531): (trypsin like peroxisomal matrix peptidase 1) This gene encodes a protease that removes the N-terminal peroxisomal targeting signal (PTS2) from proteins produced in the cytosol, thereby facilitating their import into the peroxisome. The encoded protein is also capable of removing the C-terminal peroxisomal targeting signal (PTS1) from proteins in the peroxisomal matrix. The full-length protein undergoes self-cleavage to produce shorter, potentially inactive, peptides. Alternative splicing results in multiple transcript variants for this gene. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173555.4. 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
	TYSND1	NM_173555.4	MANE Select	c.1167-267A>C		intron	N/A	NP_775826.2
	TYSND1	NM_001040273.3		c.1166+1182A>C		intron	N/A	NP_001035363.1
	TYSND1	NR_073580.2		n.48+2414A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYSND1	ENST00000287078.7	TSL:1 MANE Select	c.1167-267A>C		intron	N/A	ENSP00000287078.6
	TYSND1	ENST00000335494.5	TSL:1	c.1166+1182A>C		intron	N/A	ENSP00000335673.5
	TYSND1	ENST00000494143.5	TSL:2	n.597A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.41
PhyloP100		-0.19

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: rs3763735; hg19: chr10-71903995;