Variant 10-70142835-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000287078.7(TYSND1):c.1316T>C(p.Val439Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,488 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TYSND1
ENST00000287078.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Variant links:

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]

TYSND1 links:

TYSND1 (HGNC:):

TYSND1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYSND1	NM_173555.4 linkuse as main transcript	c.1316T>C	p.Val439Ala	missense_variant	3/4	ENST00000287078.7	NP_775826.2	Q2T9J0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TYSND1	ENST00000287078.7 linkuse as main transcript	c.1316T>C	p.Val439Ala	missense_variant	3/4	1	NM_173555.4	ENSP00000287078.6	Q2T9J0-1
TYSND1	ENST00000335494.5 linkuse as main transcript	c.1166+2586T>C		intron_variant		1		ENSP00000335673.5	Q2T9J0-2
TYSND1	ENST00000479086.1 linkuse as main transcript	n.294T>C		non_coding_transcript_exon_variant	3/4	2
TYSND1	ENST00000494143.5 linkuse as main transcript	n.1013T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461488

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The c.1316T>C (p.V439A) alteration is located in exon 3 (coding exon 3) of the TYSND1 gene. This alteration results from a T to C substitution at nucleotide position 1316, causing the valine (V) at amino acid position 439 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.67

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.22

MutationAssessor

Benign

0.85

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.68

Sift

Benign

0.041

Sift4G

Uncertain

0.047

Polyphen

0.99

Vest4

0.62

MutPred

0.61

Loss of sheet (P = 0.0357);

MVP

0.87

ClinPred

0.95

GERP RS

4.0

Varity_R

0.14

gMVP

0.62

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over