chr22-41256727-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_002883.4(RANGAP1):c.872G>C(p.Gly291Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000176 in 1,613,886 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 3 hom. )
Consequence
RANGAP1
NM_002883.4 missense
NM_002883.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
RANGAP1 (HGNC:9854): (Ran GTPase activating protein 1) This gene encodes a protein that associates with the nuclear pore complex and participates in the regulation of nuclear transport. The encoded protein interacts with Ras-related nuclear protein 1 (RAN) and regulates guanosine triphosphate (GTP)-binding and exchange. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012643188).
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RANGAP1 | NM_002883.4 | c.872G>C | p.Gly291Ala | missense_variant | 8/16 | ENST00000356244.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RANGAP1 | ENST00000356244.8 | c.872G>C | p.Gly291Ala | missense_variant | 8/16 | 1 | NM_002883.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152202Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
13
AN:
152202
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000420 AC: 105AN: 249930Hom.: 2 AF XY: 0.000569 AC XY: 77AN XY: 135332
GnomAD3 exomes
AF:
AC:
105
AN:
249930
Hom.:
AF XY:
AC XY:
77
AN XY:
135332
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000185 AC: 271AN: 1461568Hom.: 3 Cov.: 31 AF XY: 0.000263 AC XY: 191AN XY: 727122
GnomAD4 exome
AF:
AC:
271
AN:
1461568
Hom.:
Cov.:
31
AF XY:
AC XY:
191
AN XY:
727122
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74488
GnomAD4 genome
?
AF:
AC:
13
AN:
152318
Hom.:
Cov.:
32
AF XY:
AC XY:
12
AN XY:
74488
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
58
Asia WGS
AF:
AC:
8
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 08, 2023 | The c.872G>C (p.G291A) alteration is located in exon 8 (coding exon 7) of the RANGAP1 gene. This alteration results from a G to C substitution at nucleotide position 872, causing the glycine (G) at amino acid position 291 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Loss of catalytic residue at L292 (P = 0.0882);Loss of catalytic residue at L292 (P = 0.0882);Loss of catalytic residue at L292 (P = 0.0882);
MVP
MPC
0.28
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at