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GeneBe

9-82982700-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152573.4(RASEF):c.2200A>G(p.Met734Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,446,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RASEF
NM_152573.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07
Variant links:
Genes affected
RASEF (HGNC:26464): (RAS and EF-hand domain containing) This gene is a member of the Rab family of GTPases that are involved in regulation of membrane traffic. The encoded protein contains an N-terminal EF-hand domain, a coiled-coil motif and a C-terminal Rab domain. A potential role as tumor suppressor has been indicated for this gene. [provided by RefSeq, Nov 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14602026).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RASEFNM_152573.4 linkuse as main transcriptc.2200A>G p.Met734Val missense_variant 17/17 ENST00000376447.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RASEFENST00000376447.4 linkuse as main transcriptc.2200A>G p.Met734Val missense_variant 17/171 NM_152573.4 P1Q8IZ41-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1446612
Hom.:
0
Cov.:
27
AF XY:
0.00000277
AC XY:
2
AN XY:
720802
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.11e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsOct 02, 2023The c.2200A>G (p.M734V) alteration is located in exon 17 (coding exon 17) of the RASEF gene. This alteration results from a A to G substitution at nucleotide position 2200, causing the methionine (M) at amino acid position 734 to be replaced by a valine (V). 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
0.099
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.26
Cadd
Benign
18
Dann
Benign
0.94
DEOGEN2
Benign
0.0046
T
Eigen
Benign
-0.14
Eigen_PC
Benign
0.031
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.2
M
MutationTaster
Benign
0.99
D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.80
N
REVEL
Benign
0.099
Sift
Benign
0.15
T
Sift4G
Benign
0.56
T
Polyphen
0.053
B
Vest4
0.20
MutPred
0.15
Gain of methylation at K735 (P = 0.0323);
MVP
0.54
MPC
0.20
ClinPred
0.57
D
GERP RS
5.0
Varity_R
0.23
gMVP
0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-85597615; API