14-35683971-T-G

Variant summary

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

The NM_001346249.2(RALGAPA1):​c.4309A>C​(p.Thr1437Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RALGAPA1
NM_001346249.2 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.214
Variant links:
Genes affected
RALGAPA1 (HGNC:17770): (Ral GTPase activating protein catalytic subunit alpha 1) This gene encodes a major subunit of the RAL-GTPase activating protein. A similar protein in mouse binds E12, a transcriptional regulator of immunoglobulin genes. The mouse protein also functions in skeletal muscle by binding to the regulatory 14-3-3 proteins upon stimulation with insulin or muscle contraction. A pseudogene of this gene has been identified on chromosome 9. [provided by RefSeq, Oct 2016]

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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=0.08192769).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RALGAPA1NM_001346249.2 linkc.4309A>C p.Thr1437Pro missense_variant Exon 21 of 42 ENST00000680220.1 NP_001333178.1 Q6GYQ0A0A7P0TAR5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RALGAPA1ENST00000680220.1 linkc.4309A>C p.Thr1437Pro missense_variant Exon 21 of 42 NM_001346249.2 ENSP00000506280.1 A0A7P0TAR5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Uncertain
0.056
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.015
T;.;T;.;.
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.52
T;T;T;T;T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.082
T;T;T;T;T
MetaSVM
Benign
-0.36
T
MutationAssessor
Benign
0.69
N;N;.;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.75
N;N;.;N;N
REVEL
Uncertain
0.37
Sift
Benign
0.19
T;T;.;T;T
Sift4G
Benign
0.29
T;T;.;T;T
Polyphen
0.0
B;B;.;.;B
Vest4
0.10
MutPred
0.072
Gain of phosphorylation at T933 (P = 0.151);Gain of phosphorylation at T933 (P = 0.151);.;.;.;
MVP
0.45
MPC
0.90
ClinPred
0.060
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.16
gMVP
0.11

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: rs2274068; hg19: chr14-36153177; API