chr2-132773817-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_207363.3(NCKAP5):c.5127A>G(p.Ile1709Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000344 in 1,455,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. 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. I1709T) has been classified as Uncertain significance.
Frequency
Consequence
NM_207363.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCKAP5 | NM_207363.3 | c.5127A>G | p.Ile1709Met | missense_variant, splice_region_variant | 16/20 | ENST00000409261.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCKAP5 | ENST00000409261.6 | c.5127A>G | p.Ile1709Met | missense_variant, splice_region_variant | 16/20 | 5 | NM_207363.3 | P1 | |
ENST00000651100.1 | n.458-40784T>C | intron_variant, non_coding_transcript_variant | |||||||
NCKAP5 | ENST00000409213.5 | c.1170A>G | p.Ile390Met | missense_variant, splice_region_variant | 14/18 | 5 | |||
NCKAP5 | ENST00000473859.1 | n.262+7235A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000124 AC: 3AN: 242788Hom.: 0 AF XY: 0.00000760 AC XY: 1AN XY: 131616
GnomAD4 exome AF: 0.00000344 AC: 5AN: 1455556Hom.: 0 Cov.: 29 AF XY: 0.00000691 AC XY: 5AN XY: 723896
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.5127A>G (p.I1709M) alteration is located in exon 16 (coding exon 14) of the NCKAP5 gene. This alteration results from a A to G substitution at nucleotide position 5127, causing the isoleucine (I) at amino acid position 1709 to be replaced by a methionine (M). 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