22-41249402-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002883.4(RANGAP1):c.1622C>T(p.Ala541Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002883.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RANGAP1 | NM_002883.4 | c.1622C>T | p.Ala541Val | missense_variant | 15/16 | ENST00000356244.8 | NP_002874.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RANGAP1 | ENST00000356244.8 | c.1622C>T | p.Ala541Val | missense_variant | 15/16 | 1 | NM_002883.4 | ENSP00000348577.3 | ||
RANGAP1 | ENST00000405486.5 | c.1622C>T | p.Ala541Val | missense_variant | 16/17 | 1 | ENSP00000385866.1 | |||
RANGAP1 | ENST00000455915.6 | c.1622C>T | p.Ala541Val | missense_variant | 14/15 | 1 | ENSP00000401470.2 | |||
RANGAP1 | ENST00000705116.1 | c.1622C>T | p.Ala541Val | missense_variant | 15/16 | ENSP00000516069.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152274Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250630Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135640
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461738Hom.: 0 Cov.: 30 AF XY: 0.0000536 AC XY: 39AN XY: 727188
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152274Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74392
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.1622C>T (p.A541V) alteration is located in exon 15 (coding exon 14) of the RANGAP1 gene. This alteration results from a C to T substitution at nucleotide position 1622, causing the alanine (A) at amino acid position 541 to be replaced by a valine (V). 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