rs8192556
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_002500.5(NEUROD1):c.590C>A(p.Pro197His) variant causes a missense change. The variant allele was found at a frequency of 0.0218 in 1,614,140 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002500.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEUROD1 | NM_002500.5 | c.590C>A | p.Pro197His | missense_variant | Exon 2 of 2 | ENST00000295108.4 | NP_002491.3 | |
NEUROD1 | NR_146175.2 | n.88+2159C>A | intron_variant | Intron 1 of 1 | ||||
NEUROD1 | NR_146176.2 | n.88+2159C>A | intron_variant | Intron 1 of 1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0160 AC: 2434AN: 152192Hom.: 29 Cov.: 32
GnomAD3 exomes AF: 0.0193 AC: 4852AN: 251302Hom.: 76 AF XY: 0.0204 AC XY: 2773AN XY: 135820
GnomAD4 exome AF: 0.0224 AC: 32811AN: 1461830Hom.: 416 Cov.: 30 AF XY: 0.0227 AC XY: 16507AN XY: 727204
GnomAD4 genome AF: 0.0160 AC: 2432AN: 152310Hom.: 29 Cov.: 32 AF XY: 0.0147 AC XY: 1093AN XY: 74480
ClinVar
Submissions by phenotype
not provided Benign:3
This variant is associated with the following publications: (PMID: 30259503, 31578821) -
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not specified Benign:2
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Hypoinsulinemia Uncertain:1
The role of NEUROD1 gene is known to be associated with neonatal onset diabetes due to pancreatic aplasia, leading to insulin dependence. It is associated with extra pancreatic manifestation of neurological impairment. However, no sufficient evidence is found to ascertain the role of rs8192556 variant in Diabetes Mellitus yet. -
Maturity-onset diabetes of the young type 6 Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Monogenic diabetes Benign:1
ACMG criteria: BA1 (1.9% overall MAF in gnomAD), BS2 (429 cases and 438 Controls in T2DM)= benign; REVEL 0.211 +BP4/4 predictors + PP3/6 predictors= conflicting evidence, not using -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at