1-174241635-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001366446.1(RABGAP1L):​c.695T>G​(p.Phe232Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RABGAP1L
NM_001366446.1 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Publications

0 publications found
Variant links:
Genes affected
RABGAP1L (HGNC:24663): (RAB GTPase activating protein 1 like) Enables GTPase activator activity and small GTPase binding activity. Acts upstream of or within regulation of protein localization. Located in Golgi apparatus; early endosome; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RABGAP1LNM_001366446.1 linkc.695T>G p.Phe232Cys missense_variant Exon 5 of 26 ENST00000681986.1 NP_001353375.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RABGAP1LENST00000681986.1 linkc.695T>G p.Phe232Cys missense_variant Exon 5 of 26 NM_001366446.1 ENSP00000507884.1 A0A804HKD7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.695T>G (p.F232C) alteration is located in exon 1 (coding exon 1) of the RABGAP1L gene. This alteration results from a T to G substitution at nucleotide position 695, causing the phenylalanine (F) at amino acid position 232 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
.;T;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.87
D;D;D
MetaSVM
Benign
-0.39
T
MutationAssessor
Uncertain
2.7
.;M;.
PhyloP100
7.6
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-6.8
D;D;D
REVEL
Pathogenic
0.80
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.94
MutPred
0.55
.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.72
MPC
1.1
ClinPred
1.0
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.87
gMVP
0.80
Mutation Taster
=20/80
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs915737768; hg19: chr1-174210773; API