5-51387668-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002202.3(ISL1):c.397C>T(p.His133Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
ISL1
NM_002202.3 missense
NM_002202.3 missense
Scores
5
9
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.64
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, 0.832
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ISL1 | NM_002202.3 | c.397C>T | p.His133Tyr | missense_variant | 3/6 | ENST00000230658.12 | |
ISL1 | XM_011543380.3 | c.205C>T | p.His69Tyr | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ISL1 | ENST00000230658.12 | c.397C>T | p.His133Tyr | missense_variant | 3/6 | 1 | NM_002202.3 | P1 | |
ISL1 | ENST00000511384.1 | c.397C>T | p.His133Tyr | missense_variant | 3/6 | 5 | |||
ISL1 | ENST00000505475.3 | n.602C>T | non_coding_transcript_exon_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249306Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135310
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727240
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at