20-13221796-AGCT-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_080826.2(ISM1):c.34_36del(p.Leu12del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,285,310 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ISM1 NM_080826.2 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.796

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 20-13221796-AGCT-A is Benign according to our data. Variant chr20-13221796-AGCT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037929.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISM1	NM_080826.2	c.34_36del	p.Leu12del	inframe_deletion	1/6	ENST00000262487.5
ISM1	XM_017027680.2	c.34_36del	p.Leu12del	inframe_deletion	1/7
TASP1	XR_001754319.3	n.1369+94171_1369+94173del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISM1	ENST00000262487.5	c.34_36del	p.Leu12del	inframe_deletion	1/6	5	NM_080826.2	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 151406 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000681 AC: 875 AN: 1285310 Hom.: 0 AF XY: 0.000704 AC XY: 445 AN XY: 632376

Gnomad4 AFR exome AF: 0.000843

Gnomad4 AMR exome AF: 0.00285

Gnomad4 ASJ exome AF: 0.00148

Gnomad4 EAS exome AF: 0.000220

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.000816

Gnomad4 NFE exome AF: 0.000486

Gnomad4 OTH exome AF: 0.000963

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000132 AC: 2 AN: 151406 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73922

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000657

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.00174 AC: 6 AN: 3460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ISM1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 14, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs764390050; hg19: chr20-13202443;