5-51384694-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002202.3(ISL1):​c.182G>A​(p.Arg61Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ISL1
NM_002202.3 missense

Scores

5
9
5

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.97
Variant links:
Genes affected
ISL1 (HGNC:6132): (ISL LIM homeobox 1) This gene encodes a member of the LIM/homeodomain family of transcription factors. The encoded protein binds to the enhancer region of the insulin gene, among others, and may play an important role in regulating insulin gene expression. The encoded protein is central to the development of pancreatic cell lineages and may also be required for motor neuron generation. Mutations in this gene have been associated with maturity-onset diabetes of the young. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ISL1NM_002202.3 linkuse as main transcriptc.182G>A p.Arg61Lys missense_variant 2/6 ENST00000230658.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ISL1ENST00000230658.12 linkuse as main transcriptc.182G>A p.Arg61Lys missense_variant 2/61 NM_002202.3 P1
ISL1ENST00000511384.1 linkuse as main transcriptc.182G>A p.Arg61Lys missense_variant 2/65

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ISL1-related disorder Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesSep 05, 2024The ISL1 c.182G>A variant is predicted to result in the amino acid substitution p.Arg61Lys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.39
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
32
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.77
D;D
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Uncertain
0.13
D
MutationAssessor
Benign
0.64
N;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-2.3
N;N
REVEL
Uncertain
0.58
Sift
Benign
0.53
T;T
Sift4G
Benign
0.13
T;T
Polyphen
0.86
P;.
Vest4
0.72
MutPred
0.74
Gain of methylation at R61 (P = 0.0095);Gain of methylation at R61 (P = 0.0095);
MVP
0.91
MPC
1.2
ClinPred
0.93
D
GERP RS
6.2
Varity_R
0.60
gMVP
0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-50680528; API