7-150467205-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_175571.4(GIMAP8):​c.507C>A​(p.Asn169Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GIMAP8
NM_175571.4 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GIMAP8NM_175571.4 linkuse as main transcriptc.507C>A p.Asn169Lys missense_variant 2/5 ENST00000307271.4 NP_783161.1 Q8ND71
GIMAP8XM_005249950.5 linkuse as main transcriptc.507C>A p.Asn169Lys 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.507C>A p.Asn169Lys missense_variant 2/51 NM_175571.4 ENSP00000305107.3 Q8ND71

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251420
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461894
Hom.:
0
Cov.:
33
AF XY:
0.0000179
AC XY:
13
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

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 GeneticsDec 18, 2023The c.507C>A (p.N169K) alteration is located in exon 2 (coding exon 1) of the GIMAP8 gene. This alteration results from a C to A substitution at nucleotide position 507, causing the asparagine (N) at amino acid position 169 to be replaced by a lysine (K). 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
Uncertain
0.37
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.058
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.011
T
MetaRNN
Pathogenic
0.77
D
MetaSVM
Uncertain
-0.024
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.28
Sift
Uncertain
0.0030
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.42
MutPred
0.74
Gain of methylation at N169 (P = 0.0024);
MVP
0.74
MPC
0.62
ClinPred
0.99
D
GERP RS
3.4
Varity_R
0.39
gMVP
0.47

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: rs776872577; hg19: chr7-150164293; API