X-70283356-T-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001363807.1(RAB41):āc.326T>Cā(p.Val109Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000166 in 1,202,040 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000089 ( 0 hom., 1 hem., cov: 23)
Exomes š: 0.000017 ( 0 hom. 4 hem. )
Consequence
RAB41
NM_001363807.1 missense
NM_001363807.1 missense
Scores
3
8
6
Clinical Significance
Conservation
PhyloP100: 5.35
Genes affected
RAB41 (HGNC:18293): (RAB41, member RAS oncogene family) This gene encodes a small GTP-binding protein that belongs to the largest family within the Ras superfamily. These proteins function as regulators of membrane trafficking. They cycle between inactive GDP-bound and activated GTP-bound states, which is controlled by GTP hydrolysis-activating proteins (GAPs). This family member can be activated by the GAP protein RN-Tre, and it is localized to the Golgi complex. [provided by RefSeq, May 2010]
PDZD11 (HGNC:28034): (PDZ domain containing 11) Enables protein C-terminus binding activity. Involved in pore complex assembly. Located in basolateral plasma membrane and cytosol. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.747
BS2
High Hemizygotes in GnomAdExome4 at 4 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAB41 | NM_001363807.1 | c.326T>C | p.Val109Ala | missense_variant | 4/8 | ENST00000374473.6 | NP_001350736.1 | |
RAB41 | NM_001032726.3 | c.323T>C | p.Val108Ala | missense_variant | 4/8 | NP_001027898.2 | ||
RAB41 | XM_011530948.4 | c.326T>C | p.Val109Ala | missense_variant | 4/7 | XP_011529250.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAB41 | ENST00000374473.6 | c.326T>C | p.Val109Ala | missense_variant | 4/8 | 5 | NM_001363807.1 | ENSP00000363597.2 | ||
RAB41 | ENST00000276066.4 | c.323T>C | p.Val108Ala | missense_variant | 4/8 | 1 | ENSP00000276066.4 | |||
PDZD11 | ENST00000695560.1 | n.*97-1081A>G | intron_variant | ENSP00000512017.1 |
Frequencies
GnomAD3 genomes AF: 0.00000890 AC: 1AN: 112360Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1AN XY: 34508
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GnomAD4 exome AF: 0.0000174 AC: 19AN: 1089680Hom.: 0 Cov.: 29 AF XY: 0.0000113 AC XY: 4AN XY: 355226
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GnomAD4 genome AF: 0.00000890 AC: 1AN: 112360Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1AN XY: 34508
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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 | Dec 03, 2024 | The c.323T>C (p.V108A) alteration is located in exon 4 (coding exon 4) of the RAB41 gene. This alteration results from a T to C substitution at nucleotide position 323, causing the valine (V) at amino acid position 108 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
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of catalytic residue at V109 (P = 0.1708);.;
MVP
MPC
0.70
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at