chr4-10540602-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_052964.4(CLNK):c.494C>G(p.Pro165Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,611,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_052964.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLNK | NM_052964.4 | c.494C>G | p.Pro165Arg | missense_variant, splice_region_variant | 11/19 | ENST00000226951.11 | |
CLNK | XM_011513775.3 | c.539C>G | p.Pro180Arg | missense_variant, splice_region_variant | 11/19 | ||
CLNK | XM_017007684.2 | c.539C>G | p.Pro180Arg | missense_variant, splice_region_variant | 11/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLNK | ENST00000226951.11 | c.494C>G | p.Pro165Arg | missense_variant, splice_region_variant | 11/19 | 1 | NM_052964.4 | P1 | |
CLNK | ENST00000507719.1 | c.368C>G | p.Pro123Arg | missense_variant, splice_region_variant | 11/13 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152158Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 249002Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135084
GnomAD4 exome AF: 0.0000527 AC: 77AN: 1459724Hom.: 0 Cov.: 30 AF XY: 0.0000454 AC XY: 33AN XY: 726352
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152158Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 23, 2023 | The c.494C>G (p.P165R) alteration is located in exon 11 (coding exon 10) of the CLNK gene. This alteration results from a C to G substitution at nucleotide position 494, causing the proline (P) at amino acid position 165 to be replaced by an arginine (R). 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