19-19630190-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016573.4(GMIP):c.2686G>A(p.Glu896Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000812 in 1,601,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
GMIP
NM_016573.4 missense
NM_016573.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 1.42
Genes affected
GMIP (HGNC:24852): (GEM interacting protein) This gene encodes a member of the ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. The encoded protein interacts with the Ras-related protein Gem through its N-terminal domain. Separately, it interacts with RhoA through a RhoGAP domain, and stimulates RhoA-dependent GTPase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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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=0.17815718).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GMIP | NM_016573.4 | c.2686G>A | p.Glu896Lys | missense_variant | 21/21 | ENST00000203556.9 | |
GMIP | NM_001288999.2 | c.2608G>A | p.Glu870Lys | missense_variant | 20/20 | ||
GMIP | NM_001288998.2 | c.2599G>A | p.Glu867Lys | missense_variant | 20/20 | ||
GMIP | XM_005259927.3 | c.2677G>A | p.Glu893Lys | missense_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GMIP | ENST00000203556.9 | c.2686G>A | p.Glu896Lys | missense_variant | 21/21 | 1 | NM_016573.4 | P1 | |
GMIP | ENST00000587238.5 | c.2608G>A | p.Glu870Lys | missense_variant | 20/20 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000828 AC: 12AN: 1449470Hom.: 0 Cov.: 33 AF XY: 0.00000835 AC XY: 6AN XY: 718906
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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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 | Jun 29, 2023 | The c.2686G>A (p.E896K) alteration is located in exon 21 (coding exon 21) of the GMIP gene. This alteration results from a G to A substitution at nucleotide position 2686, causing the glutamic acid (E) at amino acid position 896 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of methylation at E896 (P = 0.0026);.;
MVP
MPC
ClinPred
D
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