chr19-47475435-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_007059.4(KPTN):c.1292C>A(p.Ala431Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_007059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KPTN | NM_007059.4 | c.1292C>A | p.Ala431Asp | missense_variant | 12/12 | ENST00000338134.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KPTN | ENST00000338134.8 | c.1292C>A | p.Ala431Asp | missense_variant | 12/12 | 1 | NM_007059.4 | P1 | |
ENST00000669287.1 | n.69-1027G>T | intron_variant, non_coding_transcript_variant | |||||||
KPTN | ENST00000600551.1 | n.183C>A | non_coding_transcript_exon_variant | 2/2 | 5 | ||||
KPTN | ENST00000594208.5 | c.*926C>A | 3_prime_UTR_variant, NMD_transcript_variant | 13/13 | 2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247574Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134508
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460556Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 726560
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Macrocephaly-developmental delay syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2020 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KPTN-related conditions. This variant is present in population databases (rs760334759, ExAC 0.003%). This sequence change replaces alanine with aspartic acid at codon 431 of the KPTN protein (p.Ala431Asp). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at