Variant chr7-150572333-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.807

Variant links:

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]

GIMAP4 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.263G>A	p.Gly88Asp	missense_variant	3/3	ENST00000255945.4
GIMAP4	NM_001363532.2 linkuse as main transcript	c.305G>A	p.Gly102Asp	missense_variant	3/3

Ensembl

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727174

show subpopulations

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Pathogenic

0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;.

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.69

T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.38

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over