12-54497850-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The ENST00000293373.11(NCKAP1L):c.61C>T(p.Arg21Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,124 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 (★). Synonymous variant affecting the same amino acid position (i.e. R21R) has been classified as Likely benign.
Frequency
Consequence
ENST00000293373.11 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NCKAP1L | NM_005337.5 | c.61C>T | p.Arg21Cys | missense_variant | 1/31 | ENST00000293373.11 | NP_005328.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NCKAP1L | ENST00000293373.11 | c.61C>T | p.Arg21Cys | missense_variant | 1/31 | 1 | NM_005337.5 | ENSP00000293373 | P1 | |
NCKAP1L | ENST00000547500.1 | n.85C>T | non_coding_transcript_exon_variant | 1/3 | 2 | |||||
NCKAP1L | ENST00000548221.5 | c.61C>T | p.Arg21Cys | missense_variant, NMD_transcript_variant | 1/31 | 2 | ENSP00000447246 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251438Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135900
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1460968Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 726838
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 06, 2023 | The c.61C>T (p.R21C) alteration is located in exon 1 (coding exon 1) of the NCKAP1L gene. This alteration results from a C to T substitution at nucleotide position 61, causing the arginine (R) at amino acid position 21 to be replaced by a cysteine (C). 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