5-131430969-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016340.6(RAPGEF6):ā€‹c.4355A>Gā€‹(p.Gln1452Arg) variant causes a missense change. The variant allele was found at a frequency of 0.851 in 1,614,014 control chromosomes in the GnomAD database, including 585,619 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.88 ( 59089 hom., cov: 31)
Exomes š‘“: 0.85 ( 526530 hom. )

Consequence

RAPGEF6
NM_016340.6 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83
Variant links:
Genes affected
RAPGEF6 (HGNC:20655): (Rap guanine nucleotide exchange factor 6) Enables several functions, including GTP-dependent protein binding activity; guanyl-nucleotide exchange factor activity; and phosphatidic acid binding activity. Involved in microvillus assembly; positive regulation of GTPase activity; and protein localization to plasma membrane. Located in several cellular components, including apical plasma membrane; centrosome; and endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=5.6677055E-7).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAPGEF6NM_016340.6 linkuse as main transcriptc.4355A>G p.Gln1452Arg missense_variant 26/28 ENST00000509018.6 NP_057424.3 Q8TEU7-1
RAPGEF6NM_001164386.2 linkuse as main transcriptc.4379A>G p.Gln1460Arg missense_variant 27/29 NP_001157858.1 Q8TEU7-4B2RTU6
RAPGEF6NM_001164387.2 linkuse as main transcriptc.4394A>G p.Gln1465Arg missense_variant 28/29 NP_001157859.1 Q8TEU7-3
RAPGEF6NM_001164388.2 linkuse as main transcriptc.4379A>G p.Gln1460Arg missense_variant 27/28 NP_001157860.1 Q8TEU7-5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAPGEF6ENST00000509018.6 linkuse as main transcriptc.4355A>G p.Gln1452Arg missense_variant 26/281 NM_016340.6 ENSP00000421684.1 Q8TEU7-1
ENSG00000273217ENST00000514667.1 linkuse as main transcriptc.4505A>G p.Gln1502Arg missense_variant 27/292 ENSP00000426948.1 E9PCH4

Frequencies

GnomAD3 genomes
AF:
0.879
AC:
133683
AN:
152076
Hom.:
59027
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.961
Gnomad AMI
AF:
0.903
Gnomad AMR
AF:
0.883
Gnomad ASJ
AF:
0.895
Gnomad EAS
AF:
0.890
Gnomad SAS
AF:
0.853
Gnomad FIN
AF:
0.818
Gnomad MID
AF:
0.807
Gnomad NFE
AF:
0.838
Gnomad OTH
AF:
0.867
GnomAD3 exomes
AF:
0.861
AC:
216554
AN:
251422
Hom.:
93478
AF XY:
0.857
AC XY:
116447
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.964
Gnomad AMR exome
AF:
0.891
Gnomad ASJ exome
AF:
0.893
Gnomad EAS exome
AF:
0.888
Gnomad SAS exome
AF:
0.861
Gnomad FIN exome
AF:
0.826
Gnomad NFE exome
AF:
0.838
Gnomad OTH exome
AF:
0.853
GnomAD4 exome
AF:
0.848
AC:
1240178
AN:
1461820
Hom.:
526530
Cov.:
66
AF XY:
0.848
AC XY:
616505
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.962
Gnomad4 AMR exome
AF:
0.892
Gnomad4 ASJ exome
AF:
0.892
Gnomad4 EAS exome
AF:
0.901
Gnomad4 SAS exome
AF:
0.860
Gnomad4 FIN exome
AF:
0.827
Gnomad4 NFE exome
AF:
0.840
Gnomad4 OTH exome
AF:
0.859
GnomAD4 genome
AF:
0.879
AC:
133803
AN:
152194
Hom.:
59089
Cov.:
31
AF XY:
0.878
AC XY:
65358
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.961
Gnomad4 AMR
AF:
0.883
Gnomad4 ASJ
AF:
0.895
Gnomad4 EAS
AF:
0.890
Gnomad4 SAS
AF:
0.852
Gnomad4 FIN
AF:
0.818
Gnomad4 NFE
AF:
0.838
Gnomad4 OTH
AF:
0.865
Alfa
AF:
0.851
Hom.:
87393
Bravo
AF:
0.891
TwinsUK
AF:
0.845
AC:
3135
ALSPAC
AF:
0.839
AC:
3232
ESP6500AA
AF:
0.960
AC:
4231
ESP6500EA
AF:
0.842
AC:
7240
ExAC
AF:
0.860
AC:
104390
Asia WGS
AF:
0.861
AC:
2993
AN:
3478
EpiCase
AF:
0.838
EpiControl
AF:
0.841

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.058
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
18
DANN
Benign
0.85
DEOGEN2
Benign
0.091
T;.;.;.;.
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.36
T;T;T;T;T
MetaRNN
Benign
5.7e-7
T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-2.0
N;.;.;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
0.95
N;.;N;.;N
REVEL
Benign
0.12
Sift
Benign
1.0
T;.;T;.;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;B;.;.;.
Vest4
0.10
MPC
0.18, 0.17
ClinPred
0.0089
T
GERP RS
5.2
Varity_R
0.050
gMVP
0.38

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1291602; hg19: chr5-130766662; API