7-150466844-G-T

Position:

• chr7-150466844-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_175571.4(GIMAP8):​c.146G>T​(p.Cys49Phe) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIMAP8 NM_175571.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP8	NM_175571.4	c.146G>T	p.Cys49Phe	missense_variant	2/5	ENST00000307271.4	NP_783161.1
GIMAP8	XM_005249950.5	c.146G>T	p.Cys49Phe	missense_variant	3/6		XP_005250007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP8	ENST00000307271.4	c.146G>T	p.Cys49Phe	missense_variant	2/5	1	NM_175571.4	ENSP00000305107.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Oct 25, 2022

The c.146G>T (p.C49F) alteration is located in exon 2 (coding exon 1) of the GIMAP8 gene. This alteration results from a G to T substitution at nucleotide position 146, causing the cysteine (C) at amino acid position 49 to be replaced by a phenylalanine (F). 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	0.32
BayesDel_addAF	Benign	0.0068	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0035	T
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.28
Sift	Benign	0.073	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.91		Gain of MoRF binding (P = 0.0673);
MVP		0.62
MPC		0.79
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.36
gMVP		0.48

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: chr7-150163932;