rs17191018

Variant names:

• chr20-13298549-A-G
• rs17191018
• NM_080826.2:c.878-393A>G

Variant summary

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

The NM_080826.2(ISM1):​c.878-393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 152,308 control chromosomes in the GnomAD database, including 258 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 0.050 (258 hom., cov: 33)
• Consequence: ISM1 NM_080826.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISM1	NM_080826.2	c.878-393A>G		intron_variant	Intron 5 of 5	ENST00000262487.5	NP_543016.1
ISM1	XM_017027680.2	c.877+6086A>G		intron_variant	Intron 5 of 6		XP_016883169.1
TASP1	XR_001754319.3	n.1369+17421T>C		intron_variant	Intron 14 of 14
TASP1	XR_007067463.1	n.1369+17421T>C		intron_variant	Intron 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISM1	ENST00000262487.5	c.878-393A>G		intron_variant	Intron 5 of 5	5	NM_080826.2	ENSP00000262487.3

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7548 AN: 152190 Hom.: 258 Cov.: 33

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.0917

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0598

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

GnomAD4 genome AF: 0.0496 AC: 7550 AN: 152308 Hom.: 258 Cov.: 33 AF XY: 0.0513 AC XY: 3818 AN XY: 74474

African (AFR) AF: 0.0372 AC: 1546 AN: 41562

American (AMR) AF: 0.0408 AC: 624 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3470

East Asian (EAS) AF: 0.0913 AC: 474 AN: 5190

South Asian (SAS) AF: 0.195 AC: 939 AN: 4824

European-Finnish (FIN) AF: 0.0313 AC: 332 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3298 AN: 68024

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0467 Hom.: 29

Bravo AF: 0.0486

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		0.28
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: rs17191018; hg19: chr20-13279196;