7-150628087-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024711.6(GIMAP6):​c.511G>A​(p.Gly171Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,614,018 control chromosomes in the GnomAD database, including 36,116 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.18 ( 2995 hom., cov: 33)
Exomes 𝑓: 0.21 ( 33121 hom. )

Consequence

GIMAP6
NM_024711.6 missense

Scores

3
15

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.144
Variant links:
Genes affected
GIMAP6 (HGNC:21918): (GTPase, IMAP family member 6) This gene encodes a member of the GTPases of immunity-associated proteins (GIMAP) family. GIMAP proteins contain GTP-binding and coiled-coil motifs, and may play roles in the regulation of cell survival. Decreased expression of this gene may play a role in non-small cell lung cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is found in a cluster with seven additional GIMAP genes on the long arm of chromosome 7. [provided by RefSeq, Sep 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0073738396).
BP6
Variant 7-150628087-C-T is Benign according to our data. Variant chr7-150628087-C-T is described in ClinVar as [Benign]. Clinvar id is 2688132.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GIMAP6NM_024711.6 linkc.511G>A p.Gly171Ser missense_variant Exon 3 of 3 ENST00000328902.9 NP_078987.3 Q6P9H5-1A0A090N7V4
GIMAP6NM_001244072.2 linkc.721G>A p.Gly241Ser missense_variant Exon 3 of 3 NP_001231001.1 Q6P9H5B4DH95
GIMAP6NM_001244071.2 linkc.*98G>A 3_prime_UTR_variant Exon 3 of 3 NP_001231000.1 Q6P9H5-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GIMAP6ENST00000328902.9 linkc.511G>A p.Gly171Ser missense_variant Exon 3 of 3 1 NM_024711.6 ENSP00000330374.5 Q6P9H5-1
GIMAP6ENST00000618759.4 linkc.721G>A p.Gly241Ser missense_variant Exon 3 of 3 2 ENSP00000479580.1 B4DH95
GIMAP6ENST00000493969 linkc.*98G>A 3_prime_UTR_variant Exon 3 of 3 2 ENSP00000418304.1 Q6P9H5-3

Frequencies

GnomAD3 genomes
AF:
0.183
AC:
27864
AN:
152054
Hom.:
2998
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0807
Gnomad AMI
AF:
0.232
Gnomad AMR
AF:
0.251
Gnomad ASJ
AF:
0.202
Gnomad EAS
AF:
0.175
Gnomad SAS
AF:
0.218
Gnomad FIN
AF:
0.315
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.157
GnomAD3 exomes
AF:
0.221
AC:
55397
AN:
251068
Hom.:
6655
AF XY:
0.221
AC XY:
29929
AN XY:
135682
show subpopulations
Gnomad AFR exome
AF:
0.0767
Gnomad AMR exome
AF:
0.299
Gnomad ASJ exome
AF:
0.200
Gnomad EAS exome
AF:
0.179
Gnomad SAS exome
AF:
0.228
Gnomad FIN exome
AF:
0.314
Gnomad NFE exome
AF:
0.207
Gnomad OTH exome
AF:
0.210
GnomAD4 exome
AF:
0.209
AC:
305913
AN:
1461846
Hom.:
33121
Cov.:
37
AF XY:
0.209
AC XY:
152160
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0753
Gnomad4 AMR exome
AF:
0.297
Gnomad4 ASJ exome
AF:
0.200
Gnomad4 EAS exome
AF:
0.182
Gnomad4 SAS exome
AF:
0.228
Gnomad4 FIN exome
AF:
0.309
Gnomad4 NFE exome
AF:
0.205
Gnomad4 OTH exome
AF:
0.206
GnomAD4 genome
AF:
0.183
AC:
27864
AN:
152172
Hom.:
2995
Cov.:
33
AF XY:
0.189
AC XY:
14091
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0806
Gnomad4 AMR
AF:
0.251
Gnomad4 ASJ
AF:
0.202
Gnomad4 EAS
AF:
0.175
Gnomad4 SAS
AF:
0.218
Gnomad4 FIN
AF:
0.315
Gnomad4 NFE
AF:
0.207
Gnomad4 OTH
AF:
0.157
Alfa
AF:
0.197
Hom.:
4622
Bravo
AF:
0.175
TwinsUK
AF:
0.201
AC:
745
ALSPAC
AF:
0.197
AC:
760
ESP6500AA
AF:
0.0867
AC:
382
ESP6500EA
AF:
0.204
AC:
1755
ExAC
AF:
0.213
AC:
25900
Asia WGS
AF:
0.201
AC:
701
AN:
3478
EpiCase
AF:
0.192
EpiControl
AF:
0.191

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 24, 2024
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.80
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0054
T;.
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.54
T;T
MetaRNN
Benign
0.0074
T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.8
L;.
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-3.1
D;.
REVEL
Benign
0.082
Sift
Benign
0.075
T;.
Sift4G
Uncertain
0.048
D;T
Polyphen
0.70
P;.
Vest4
0.14
MPC
0.58
ClinPred
0.030
T
GERP RS
3.4
Varity_R
0.19
gMVP
0.49

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: rs13234724; hg19: chr7-150325175; COSMIC: COSV61032401; API