chrX-102937967-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001031834.1(RAB40AL):​c.649G>A​(p.Ala217Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000083 ( 0 hom. 43 hem. )
Failed GnomAD Quality Control

Consequence

RAB40AL
NM_001031834.1 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32
Variant links:
Genes affected
RAB40AL (HGNC:25410): (RAB40A like) This gene encodes a member of the Rab40 subfamily of Rab small GTP-binding proteins that contains a C-terminal suppressors of cytokine signaling box. Disruptions in this gene are associated with Duchenne muscular dystrophy. [provided by RefSeq, Apr 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.11400846).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAB40ALNM_001031834.1 linkuse as main transcriptc.649G>A p.Ala217Thr missense_variant 1/1 ENST00000218249.7
LINC00630NR_146589.1 linkuse as main transcriptn.1910-20681G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAB40ALENST00000218249.7 linkuse as main transcriptc.649G>A p.Ala217Thr missense_variant 1/1 NM_001031834.1 P1
ENST00000413528.1 linkuse as main transcriptn.431C>T non_coding_transcript_exon_variant 2/25

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
21
AN:
111534
Hom.:
0
Cov.:
23
AF XY:
0.0000294
AC XY:
1
AN XY:
34042
FAILED QC
Gnomad AFR
AF:
0.000620
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000564
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000832
AC:
91
AN:
1093095
Hom.:
0
Cov.:
32
AF XY:
0.000119
AC XY:
43
AN XY:
360767
show subpopulations
Gnomad4 AFR exome
AF:
0.000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00136
Gnomad4 SAS exome
AF:
0.000536
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000716
Gnomad4 OTH exome
AF:
0.000109
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000188
AC:
21
AN:
111586
Hom.:
0
Cov.:
23
AF XY:
0.0000293
AC XY:
1
AN XY:
34104
show subpopulations
Gnomad4 AFR
AF:
0.000618
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000566
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000553
Hom.:
0

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 submitterclinical testingAmbry GeneticsMar 02, 2023The c.649G>A (p.A217T) alteration is located in exon 1 (coding exon 1) of the RAB40AL gene. This alteration results from a G to A substitution at nucleotide position 649, causing the alanine (A) at amino acid position 217 to be replaced by a threonine (T). 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
Benign
0.074
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.88
CADD
Benign
13
DANN
Benign
0.85
DEOGEN2
Benign
0.00076
T
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.26
N
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.062
Sift
Benign
0.81
T
Sift4G
Benign
0.92
T
Polyphen
0.0050
B
Vest4
0.19
MVP
0.65
MPC
0.47
ClinPred
0.021
T
GERP RS
-0.18
Varity_R
0.059
gMVP
0.032

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: rs767256032; hg19: chrX-102192895; API