rs6074585

Variant names:

• chr20-13294555-G-C
• rs6074585
• NM_080826.2:c.877+2092G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-13294555-G-C
• chr20-13294555-G-T

Variant summary

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

The NM_080826.2(ISM1):​c.877+2092G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,184 control chromosomes in the GnomAD database, including 1,356 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 (1356 hom., cov: 32)
• Consequence: ISM1 NM_080826.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.167
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISM1	NM_080826.2	c.877+2092G>C		intron_variant	Intron 5 of 5	ENST00000262487.5	NP_543016.1
ISM1	XM_017027680.2	c.877+2092G>C		intron_variant	Intron 5 of 6		XP_016883169.1
TASP1	XR_001754319.3	n.1369+21415C>G		intron_variant	Intron 14 of 14
TASP1	XR_007067463.1	n.1369+21415C>G		intron_variant	Intron 14 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISM1	ENST00000262487.5	c.877+2092G>C		intron_variant	Intron 5 of 5	5	NM_080826.2	ENSP00000262487.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18002 AN: 152066 Hom.: 1355 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.118 AC: 17990 AN: 152184 Hom.: 1356 Cov.: 32 AF XY: 0.114 AC XY: 8503 AN XY: 74394

African (AFR) AF: 0.0627 AC: 2602 AN: 41528

American (AMR) AF: 0.125 AC: 1906 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0778 AC: 375 AN: 4820

European-Finnish (FIN) AF: 0.101 AC: 1067 AN: 10590

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10489 AN: 68000

Other (OTH) AF: 0.153 AC: 324 AN: 2112

Alfa AF: 0.0512 Hom.: 54

Bravo AF: 0.119

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.64
PhyloP100		0.17
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: rs6074585; hg19: chr20-13275202;