chr7-150742584-C-G

Position:

• chr7-150742584-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP6

The NM_018384.5(GIMAP5):​c.445C>G​(p.Leu149Val) 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 Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIMAP5 NM_018384.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0880

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:51257): (GIMAP1-GIMAP5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GIMAP1 (GTPase, IMAP family member 1) and GIMAP5 (GTPase, IMAP family member 5) genes on chromosome 7. Alternative splicing results in multiple readthrough transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2015]

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=0.36672154).
• BP6: Variant 7-150742584-C-G is Benign according to our data. Variant chr7-150742584-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2681295.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP5	NM_018384.5	c.445C>G	p.Leu149Val	missense_variant	3/3	ENST00000358647.5	NP_060854.2
GIMAP1-GIMAP5	NM_001199577.2	c.1057C>G	p.Leu353Val	missense_variant	6/6		NP_001186506.1
GIMAP1-GIMAP5	NM_001303630.2	c.673C>G	p.Leu225Val	missense_variant	5/5		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP5	ENST00000358647.5	c.445C>G	p.Leu149Val	missense_variant	3/3	1	NM_018384.5	ENSP00000351473.3
GIMAP1-GIMAP5	ENST00000611999.4	c.1057C>G	p.Leu353Val	missense_variant	6/6	5		ENSP00000477920.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

EBV-positive nodal T- and NK-cell lymphoma Benign:1

Likely benign, no assertion criteria provided

research

Department of Clinical Pathology, School of Medicine, Fujita Health University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	.;T;T
Eigen	Benign	0.018
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	.;M;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	.;.;N
REVEL	Benign	0.16
Sift	Benign	0.21	.;.;T
Sift4G	Benign	0.15	T;T;T
Polyphen		1.0	.;D;D
Vest4		0.56
MutPred		0.60		.;Loss of stability (P = 0.0648);Loss of stability (P = 0.0648);
MVP		0.17
MPC		0.16
ClinPred		0.73	D
GERP RS		3.3
Varity_R		0.19
gMVP		0.22

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: chr7-150439672;