7-150628087-C-T

Variant names:

• chr7-150628087-C-T
• rs13234724
• NM_024711.6:c.511G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2995 hom., cov: 33)
  • Exomes 𝑓: 0.21 (33121 hom.)
• Consequence: GIMAP6 NM_024711.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.144
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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
GIMAP6	NM_024711.6	c.511G>A	p.Gly171Ser	missense_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3
GIMAP6	NM_001244072.2	c.721G>A	p.Gly241Ser	missense_variant	Exon 3 of 3		NP_001231001.1
GIMAP6	NM_001244071.2	c.*98G>A		3_prime_UTR_variant	Exon 3 of 3		NP_001231000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP6	ENST00000328902.9	c.511G>A	p.Gly171Ser	missense_variant	Exon 3 of 3	1	NM_024711.6	ENSP00000330374.5
GIMAP6	ENST00000618759.4	c.721G>A	p.Gly241Ser	missense_variant	Exon 3 of 3	2		ENSP00000479580.1
GIMAP6	ENST00000493969.2	c.*98G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000418304.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27864 AN: 152054 Hom.: 2998 Cov.: 33

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

GnomAD2 exomes AF: 0.221 AC: 55397 AN: 251068 AF XY: 0.221

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 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

African (AFR) AF: 0.0753 AC: 2522 AN: 33480

American (AMR) AF: 0.297 AC: 13280 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 5224 AN: 26136

East Asian (EAS) AF: 0.182 AC: 7221 AN: 39700

South Asian (SAS) AF: 0.228 AC: 19628 AN: 86256

European-Finnish (FIN) AF: 0.309 AC: 16496 AN: 53386

Middle Eastern (MID) AF: 0.146 AC: 843 AN: 5768

European-Non Finnish (NFE) AF: 0.205 AC: 228267 AN: 1112000

Other (OTH) AF: 0.206 AC: 12432 AN: 60396

GnomAD4 genome AF: 0.183 AC: 27864 AN: 152172 Hom.: 2995 Cov.: 33 AF XY: 0.189 AC XY: 14091 AN XY: 74386

African (AFR) AF: 0.0806 AC: 3351 AN: 41552

American (AMR) AF: 0.251 AC: 3841 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3466

East Asian (EAS) AF: 0.175 AC: 900 AN: 5146

South Asian (SAS) AF: 0.218 AC: 1052 AN: 4830

European-Finnish (FIN) AF: 0.315 AC: 3339 AN: 10590

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14093 AN: 67974

Other (OTH) AF: 0.157 AC: 332 AN: 2114

Alfa AF: 0.193 Hom.: 6231

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

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;.
PhyloP100		0.14
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
Mutation Taster		=89/11	polymorphism (auto)

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

Other links and lift over

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