NM_001202439.3:c.581T>A
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001202439.3(NCR3LG1):c.581T>A(p.Val194Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,536,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001202439.3 missense
Scores
Clinical Significance
Conservation
Publications
- diabetes mellitus, transient neonatal, 3Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
- monogenic diabetesInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- hyperinsulinemic hypoglycemia, familial, 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- diabetes mellitus, noninsulin-dependentInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- diabetes mellitus, permanent neonatal 2Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- maturity-onset diabetes of the young type 13Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- autosomal dominant hyperinsulinism due to Kir6.2 deficiencyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- DEND syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- intermediate DEND syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- maturity-onset diabetes of the youngInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- permanent neonatal diabetes mellitusInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- transient neonatal diabetes mellitusInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal recessive hyperinsulinism due to Kir6.2 deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiencyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NCR3LG1 | NM_001202439.3 | c.581T>A | p.Val194Asp | missense_variant | Exon 3 of 5 | ENST00000338965.9 | NP_001189368.1 | |
NCR3LG1 | XM_047426906.1 | c.581T>A | p.Val194Asp | missense_variant | Exon 3 of 6 | XP_047282862.1 | ||
NCR3LG1 | XM_011520074.4 | c.494T>A | p.Val165Asp | missense_variant | Exon 3 of 5 | XP_011518376.1 | ||
NCR3LG1 | XM_011520075.4 | c.494T>A | p.Val165Asp | missense_variant | Exon 3 of 5 | XP_011518377.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NCR3LG1 | ENST00000338965.9 | c.581T>A | p.Val194Asp | missense_variant | Exon 3 of 5 | 1 | NM_001202439.3 | ENSP00000341637.4 | ||
NCR3LG1 | ENST00000530403.1 | n.581T>A | non_coding_transcript_exon_variant | Exon 3 of 6 | 5 | ENSP00000434394.1 | ||||
KCNJ11 | ENST00000682764.1 | c.*51-866A>T | intron_variant | Intron 2 of 2 | ENSP00000506780.1 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152126Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000142 AC: 2AN: 141286 AF XY: 0.00 show subpopulations
GnomAD4 exome AF: 0.0000383 AC: 53AN: 1384312Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 32AN XY: 683060 show subpopulations
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74430 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.581T>A (p.V194D) alteration is located in exon 3 (coding exon 3) of the NCR3LG1 gene. This alteration results from a T to A substitution at nucleotide position 581, causing the valine (V) at amino acid position 194 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at