NM_173555.4:c.1167-267A>G

Variant names:

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

Variant summary

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

The NM_173555.4(TYSND1):​c.1167-267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 457,426 control chromosomes in the GnomAD database, including 169,454 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 0.82 (52445 hom., cov: 33)
  • Exomes 𝑓: 0.87 (117009 hom.)
• 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: 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 = 0.894 is higher than 0.05.

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>G		intron	N/A	NP_775826.2
	TYSND1	NM_001040273.3		c.1166+1182A>G		intron	N/A	NP_001035363.1
	TYSND1	NR_073580.2		n.48+2414A>G		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>G		intron	N/A	ENSP00000287078.6
	TYSND1	ENST00000335494.5	TSL:1	c.1166+1182A>G		intron	N/A	ENSP00000335673.5
	TYSND1	ENST00000494143.5	TSL:2	n.597A>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.825 AC: 125423 AN: 152088 Hom.: 52441 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.825

GnomAD4 exome AF: 0.873 AC: 266574 AN: 305220 Hom.: 117009 Cov.: 5 AF XY: 0.869 AC XY: 138845 AN XY: 159822

African (AFR) AF: 0.681 AC: 5715 AN: 8396

American (AMR) AF: 0.856 AC: 9152 AN: 10688

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 6316 AN: 8398

East Asian (EAS) AF: 0.780 AC: 12256 AN: 15710

South Asian (SAS) AF: 0.806 AC: 27702 AN: 34372

European-Finnish (FIN) AF: 0.937 AC: 13999 AN: 14942

Middle Eastern (MID) AF: 0.807 AC: 1036 AN: 1284

European-Non Finnish (NFE) AF: 0.904 AC: 176287 AN: 194958

Other (OTH) AF: 0.857 AC: 14111 AN: 16472

GnomAD4 genome AF: 0.824 AC: 125468 AN: 152206 Hom.: 52445 Cov.: 33 AF XY: 0.824 AC XY: 61378 AN XY: 74446

African (AFR) AF: 0.678 AC: 28142 AN: 41486

American (AMR) AF: 0.842 AC: 12879 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2611 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3987 AN: 5188

South Asian (SAS) AF: 0.801 AC: 3859 AN: 4820

European-Finnish (FIN) AF: 0.939 AC: 9963 AN: 10612

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61214 AN: 68016

Other (OTH) AF: 0.819 AC: 1730 AN: 2112

Alfa AF: 0.871 Hom.: 32287

Bravo AF: 0.812

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.45
PhyloP100		-0.19
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: rs3763735; hg19: chr10-71903995; COSMIC: COSV107278611; COSMIC: COSV107278611;