chr7-150742422-G-C

Position:

• chr7-150742422-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018384.5(GIMAP5):​c.283G>C​(p.Glu95Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIMAP5 NM_018384.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.686

Genes affected

GIMAP5 (HGNC:18005): (GTPase, IMAP family member 5) 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. This gene encodes an antiapoptotic protein that functions in T-cell survival. Polymorphisms in this gene are associated with systemic lupus erythematosus. Read-through transcription exists between this gene and the neighboring upstream GIMAP1 (GTPase, IMAP family member 1) gene. [provided by RefSeq, Dec 2010]

GIMAP1-GIMAP5 (HGNC:):

ACMG classification

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=0.1282593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP5	NM_018384.5	c.283G>C	p.Glu95Gln	missense_variant	3/3	ENST00000358647.5
GIMAP1-GIMAP5	NM_001199577.2	c.895G>C	p.Glu299Gln	missense_variant	6/6
GIMAP1-GIMAP5	NM_001303630.2	c.511G>C	p.Glu171Gln	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMAP5	ENST00000358647.5	c.283G>C	p.Glu95Gln	missense_variant	3/3	1	NM_018384.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.895G>C (p.E299Q) alteration is located in exon 6 (coding exon 5) of the GIMAP1-GIMAP5 gene. This alteration results from a G to C substitution at nucleotide position 895, causing the glutamic acid (E) at amino acid position 299 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	.;T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.52	T;.;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	.;.;N
REVEL	Benign	0.091
Sift	Benign	0.27	.;.;T
Sift4G	Benign	0.57	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.16
MutPred		0.42		.;Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.13
MPC		0.10
ClinPred		0.66	D
GERP RS		3.8
Varity_R		0.11
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150439510; COSMIC: COSV57529874; COSMIC: COSV57529874;