rs200209474

Variant names:

• chr5-51389708-A-G
• NM_002202.3:c.541A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-51389708-A-G
• chr5-51389708-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002202.3(ISL1):​c.541A>G​(p.Thr181Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ISL1 NM_002202.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35148558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISL1	NM_002202.3	c.541A>G	p.Thr181Ala	missense_variant	Exon 4 of 6	ENST00000230658.12	NP_002193.2
ISL1	XM_011543380.3	c.349A>G	p.Thr117Ala	missense_variant	Exon 3 of 5		XP_011541682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISL1	ENST00000230658.12	c.541A>G	p.Thr181Ala	missense_variant	Exon 4 of 6	1	NM_002202.3	ENSP00000230658.7
ISL1	ENST00000511384.1	c.541A>G	p.Thr181Ala	missense_variant	Exon 4 of 6	5		ENSP00000422676.1
ISL1	ENST00000505475.3	n.746A>G		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461554 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.47
Sift	Benign	0.31	T;T
Sift4G	Benign	0.78	T;T
Polyphen		0.50	P;.
Vest4		0.37
MutPred		0.22		Loss of glycosylation at T181 (P = 0.014);Loss of glycosylation at T181 (P = 0.014);
MVP		0.78
MPC		1.1
ClinPred		0.88	D
GERP RS		6.0
Varity_R		0.26
gMVP		0.73

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: chr5-50685542;