chr6-150800780-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001029884.3(PLEKHG1):c.691C>T(p.Arg231Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,613,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
PLEKHG1
NM_001029884.3 missense
NM_001029884.3 missense
Scores
1
8
5
Clinical Significance
Conservation
PhyloP100: 4.00
Genes affected
PLEKHG1 (HGNC:20884): (pleckstrin homology and RhoGEF domain containing G1) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHG1 | NM_001029884.3 | c.691C>T | p.Arg231Cys | missense_variant | 7/17 | ENST00000696526.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHG1 | ENST00000696526.1 | c.691C>T | p.Arg231Cys | missense_variant | 7/17 | NM_001029884.3 | P1 | ||
PLEKHG1 | ENST00000475490.1 | c.232C>T | p.Arg78Cys | missense_variant, NMD_transcript_variant | 4/15 | 1 | |||
PLEKHG1 | ENST00000358517.6 | c.691C>T | p.Arg231Cys | missense_variant | 6/16 | 5 | P1 | ||
PLEKHG1 | ENST00000644968.1 | c.691C>T | p.Arg231Cys | missense_variant | 6/16 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152190Hom.: 0 Cov.: 32
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?
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251472Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135912
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GnomAD4 exome AF: 0.000129 AC: 189AN: 1460992Hom.: 0 Cov.: 31 AF XY: 0.000131 AC XY: 95AN XY: 726878
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74334
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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 submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.691C>T (p.R231C) alteration is located in exon 7 (coding exon 5) of the PLEKHG1 gene. This alteration results from a C to T substitution at nucleotide position 691, causing the arginine (R) at amino acid position 231 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Polyphen
D;D
Vest4
0.42
MVP
0.84
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at