7-150572333-G-A

Variant summary

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

The NM_018326.3(GIMAP4):c.263G>A(p.Gly88Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GIMAP4 NM_018326.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.807

Genes affected

GIMAP4 (HGNC:21872): (GTPase, IMAP family member 4) This gene encodes a protein belonging to the GTP-binding superfamily and to the immuno-associated nucleotide (IAN) subfamily of nucleotide-binding proteins. The encoded protein of this gene may be negatively regulated by T-cell acute lymphocytic leukemia 1 (TAL1). 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, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP4	NM_018326.3	c.263G>A	p.Gly88Asp	missense_variant	3/3	ENST00000255945.4
GIMAP4	NM_001363532.2	c.305G>A	p.Gly102Asp	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMAP4	ENST00000255945.4	c.263G>A	p.Gly88Asp	missense_variant	3/3	1	NM_018326.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461746 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 727174

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

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 21, 2023

The c.263G>A (p.G88D) alteration is located in exon 3 (coding exon 2) of the GIMAP4 gene. This alteration results from a G to A substitution at nucleotide position 263, causing the glycine (G) at amino acid position 88 to be replaced by an aspartic acid (D). 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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.6	D;D;D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D;D;T
Sift4G	Pathogenic	0.0	D;D;T
Polyphen		1.0	D;D;.
Vest4		0.41
MutPred		0.88		.;Gain of catalytic residue at G102 (P = 0.0409);Gain of catalytic residue at G102 (P = 0.0409);
MVP		0.97
MPC		0.38
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.91
gMVP		0.89

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: chr7-150269421; COSMIC: COSV55431534;