chr7-142942883-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000420.3(KEL):c.1933G>T(p.Ala645Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,876 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A645V) has been classified as Uncertain significance.
Frequency
Consequence
NM_000420.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KEL | NM_000420.3 | c.1933G>T | p.Ala645Ser | missense_variant | 17/19 | ENST00000355265.7 | |
KEL | XM_005249993.2 | c.1969G>T | p.Ala657Ser | missense_variant | 17/19 | ||
KEL | XM_047420357.1 | c.1822G>T | p.Ala608Ser | missense_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KEL | ENST00000355265.7 | c.1933G>T | p.Ala645Ser | missense_variant | 17/19 | 1 | NM_000420.3 | P1 | |
KEL | ENST00000470850.1 | n.233G>T | non_coding_transcript_exon_variant | 3/4 | 2 | ||||
KEL | ENST00000478969.1 | n.272G>T | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461876Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2023 | The c.1933G>T (p.A645S) alteration is located in exon 17 (coding exon 17) of the KEL gene. This alteration results from a G to T substitution at nucleotide position 1933, causing the alanine (A) at amino acid position 645 to be replaced by a serine (S). 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