7-150466964-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_175571.4(GIMAP8):ā€‹c.266T>Gā€‹(p.Leu89Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,198 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.000028 ( 0 hom. )

Consequence

GIMAP8
NM_175571.4 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59
Variant links:
Genes affected
GIMAP8 (HGNC:21792): (GTPase, IMAP family member 8) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. In humans, the IAN subfamily genes are located in a cluster at 7q36.1. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41444713).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GIMAP8NM_175571.4 linkuse as main transcriptc.266T>G p.Leu89Arg missense_variant 2/5 ENST00000307271.4 NP_783161.1 Q8ND71
GIMAP8XM_005249950.5 linkuse as main transcriptc.266T>G p.Leu89Arg missense_variant 3/6 XP_005250007.1 Q8ND71

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GIMAP8ENST00000307271.4 linkuse as main transcriptc.266T>G p.Leu89Arg missense_variant 2/51 NM_175571.4 ENSP00000305107.3 Q8ND71

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000151
AC:
38
AN:
251404
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135868
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00101
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000280
AC:
41
AN:
1461870
Hom.:
0
Cov.:
33
AF XY:
0.0000261
AC XY:
19
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000894
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152328
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000965
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10

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 submitterclinical testingAmbry GeneticsAug 02, 2021The c.266T>G (p.L89R) alteration is located in exon 2 (coding exon 1) of the GIMAP8 gene. This alteration results from a T to G substitution at nucleotide position 266, causing the leucine (L) at amino acid position 89 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.044
T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-3.2
D
REVEL
Benign
0.21
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.68
MVP
0.62
MPC
0.77
ClinPred
0.27
T
GERP RS
4.5
Varity_R
0.57
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs140677657; hg19: chr7-150164052; API