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GeneBe

20-13279762-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_080826.2(ISM1):c.507C>G(p.Ala169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ISM1
NM_080826.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.241
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 20-13279762-C-G is Benign according to our data. Variant chr20-13279762-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3047170.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.241 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ISM1NM_080826.2 linkuse as main transcriptc.507C>G p.Ala169= synonymous_variant 3/6 ENST00000262487.5
ISM1XM_017027680.2 linkuse as main transcriptc.507C>G p.Ala169= synonymous_variant 3/7
TASP1XR_001754319.3 linkuse as main transcriptn.1369+36208G>C intron_variant, non_coding_transcript_variant
TASP1XR_007067463.1 linkuse as main transcriptn.1370-13580G>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ISM1ENST00000262487.5 linkuse as main transcriptc.507C>G p.Ala169= synonymous_variant 3/65 NM_080826.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000985
AC:
15
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000923
AC:
23
AN:
249056
Hom.:
0
AF XY:
0.000104
AC XY:
14
AN XY:
135124
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000168
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000122
AC:
179
AN:
1461706
Hom.:
0
Cov.:
33
AF XY:
0.000133
AC XY:
97
AN XY:
727138
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:
0.0000116
Gnomad4 FIN exome
AF:
0.000169
Gnomad4 NFE exome
AF:
0.000148
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000985
AC:
15
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.0000941
AC XY:
7
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000175
Hom.:
0
Bravo
AF:
0.0000907
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

ISM1-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesApr 22, 2019This 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

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
0.57
Dann
Benign
0.65

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373209074; hg19: chr20-13260409; API