chr1-6470307-C-G

Variant summary

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

The NM_020631.6(PLEKHG5):​c.1729G>C​(p.Ala577Pro) 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. 12/21 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. A577T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PLEKHG5
NM_020631.6 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.975
Variant links:
Genes affected
PLEKHG5 (HGNC:29105): (pleckstrin homology and RhoGEF domain containing G5) This gene encodes a protein that activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in this gene are associated with autosomal recessive distal spinal muscular atrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 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=0.23661616).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLEKHG5NM_020631.6 linkuse as main transcriptc.1729G>C p.Ala577Pro missense_variant 16/21 ENST00000377728.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLEKHG5ENST00000377728.8 linkuse as main transcriptc.1729G>C p.Ala577Pro missense_variant 16/212 NM_020631.6 P2O94827-5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.62
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
.;.;.;.;.;.;.;.;T;T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.96
D;.;D;D;D;D;.;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.24
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
.;.;.;.;.;.;.;.;L;.
MutationTaster
Benign
0.99
N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.6
D;D;D;D;D;D;D;D;D;D
REVEL
Benign
0.063
Sift
Benign
0.087
T;T;T;T;T;T;T;T;T;T
Sift4G
Uncertain
0.020
D;D;D;D;D;D;D;D;D;D
Polyphen
0.98, 0.92, 0.94, 0.15
.;.;.;.;D;P;.;.;P;B
Vest4
0.45
MutPred
0.31
.;.;.;.;.;.;.;.;Gain of glycosylation at A633 (P = 0.0215);.;
MVP
0.22
MPC
1.0
ClinPred
0.96
D
GERP RS
2.0
Varity_R
0.35
gMVP
0.62

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: rs143545780; hg19: chr1-6530367; API