chr19-15451853-C-T

Variant summary

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

The NM_022904.3(RASAL3):​c.2978G>A​(p.Gly993Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G993A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RASAL3
NM_022904.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.680
Variant links:
Genes affected
RASAL3 (HGNC:26129): (RAS protein activator like 3) This gene belongs to the Ras GTPase-activating proteins (RasGAP) family and encodes a protein with pleckstrin homology (PH), C2, and Ras GTPase-activation protein (RasGAP) domains. This protein is localized near or at the plasma membrane when expressed exogenously. Reduced expression of this gene in some cell lines resulted in increased levels of the active form of Ras (Ras-GTP), suggesting that this gene may play a role in negatively regulating the Ras signaling pathway. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2017]

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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=0.08108887).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RASAL3NM_022904.3 linkc.2978G>A p.Gly993Glu missense_variant Exon 18 of 18 ENST00000343625.12 NP_075055.1 Q86YV0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RASAL3ENST00000343625.12 linkc.2978G>A p.Gly993Glu missense_variant Exon 18 of 18 2 NM_022904.3 ENSP00000341905.5 Q86YV0-1
RASAL3ENST00000599694.1 linkc.1277G>A p.Gly426Glu missense_variant Exon 7 of 7 5 ENSP00000468841.1 M0QX12
RASAL3ENST00000609274 linkc.*801G>A 3_prime_UTR_variant Exon 4 of 4 2 ENSP00000476634.1 V9GYD1
RASAL3ENST00000602101.6 linkn.4049G>A non_coding_transcript_exon_variant Exon 16 of 16 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1456362
Hom.:
0
Cov.:
31
AF XY:
0.00000277
AC XY:
2
AN XY:
723312
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
7.1
DANN
Benign
0.84
DEOGEN2
Benign
0.0043
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.094
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.010
Sift
Benign
0.073
T
Sift4G
Benign
0.28
T
Polyphen
0.029
B
Vest4
0.14
MutPred
0.11
Loss of MoRF binding (P = 0.0447);
MVP
0.26
MPC
0.010
ClinPred
0.10
T
GERP RS
2.5
Varity_R
0.053
gMVP
0.16

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: rs759161243; hg19: chr19-15562664; COSMIC: COSV54607782; COSMIC: COSV54607782; API