chr3-52478461-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_007184.4(NISCH):c.1186C>T(p.Arg396Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,614,158 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R396Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_007184.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NISCH | NM_007184.4 | c.1186C>T | p.Arg396Trp | missense_variant | 11/21 | ENST00000345716.9 | |
NISCH | NM_001276293.2 | c.1186C>T | p.Arg396Trp | missense_variant | 11/13 | ||
NISCH | NM_001276294.2 | c.1186C>T | p.Arg396Trp | missense_variant | 11/14 | ||
NISCH | XM_047447373.1 | c.1186C>T | p.Arg396Trp | missense_variant | 11/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NISCH | ENST00000345716.9 | c.1186C>T | p.Arg396Trp | missense_variant | 11/21 | 1 | NM_007184.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000217 AC: 33AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000255 AC: 64AN: 251454Hom.: 1 AF XY: 0.000177 AC XY: 24AN XY: 135906
GnomAD4 exome AF: 0.000468 AC: 684AN: 1461880Hom.: 3 Cov.: 33 AF XY: 0.000417 AC XY: 303AN XY: 727238
GnomAD4 genome ? AF: 0.000217 AC: 33AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74466
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 11, 2021 | The c.1186C>T (p.R396W) alteration is located in exon 11 (coding exon 11) of the NISCH gene. This alteration results from a C to T substitution at nucleotide position 1186, causing the arginine (R) at amino acid position 396 to be replaced by a tryptophan (W). 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