rs13433297

Variant names:

• chr20-13319088-G-A
• rs13433297
• XM_017027680.2:c.878-5978G>A

Variant summary

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

The XM_017027680.2(ISM1):​c.878-5978G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,150 control chromosomes in the GnomAD database, including 1,528 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 0.12 (1528 hom., cov: 32)
• Consequence: ISM1 XM_017027680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 2 publications found

Genes affected

ISM1 (HGNC:16213): (isthmin 1) Predicted to be involved in negative regulation of angiogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

TASP1 (HGNC:15859): (taspase 1) This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TASP1 Gene-Disease associations (from GenCC):

• Suleiman-El-Hattab syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

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 = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISM1	XM_017027680.2	c.878-5978G>A		intron_variant	Intron 5 of 6		XP_016883169.1
TASP1	XM_047440269.1	c.1171-3033C>T		intron_variant	Intron 13 of 13		XP_047296225.1
TASP1	XR_001754319.3	n.1284-3033C>T		intron_variant	Intron 13 of 14
TASP1	XR_007067463.1	n.1284-3033C>T		intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18105 AN: 152032 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.119 AC: 18109 AN: 152150 Hom.: 1528 Cov.: 32 AF XY: 0.117 AC XY: 8694 AN XY: 74392

African (AFR) AF: 0.0315 AC: 1308 AN: 41532

American (AMR) AF: 0.0880 AC: 1344 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 664 AN: 3466

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5182

South Asian (SAS) AF: 0.0625 AC: 301 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1950 AN: 10586

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12189 AN: 67976

Other (OTH) AF: 0.107 AC: 226 AN: 2110

Alfa AF: 0.160 Hom.: 1088

Bravo AF: 0.107

Asia WGS AF: 0.0470 AC: 164 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	3.8
DANN	Benign	0.61
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13433297; hg19: chr20-13299735;