Variant 7-150572422-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018326.3(GIMAP4):c.352C>T(p.Leu118Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

GIMAP4
NM_018326.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.287

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046427548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP4	NM_018326.3 linkuse as main transcript	c.352C>T	p.Leu118Phe	missense_variant	3/3	ENST00000255945.4
GIMAP4	NM_001363532.2 linkuse as main transcript	c.394C>T	p.Leu132Phe	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMAP4	ENST00000255945.4 linkuse as main transcript	c.352C>T	p.Leu118Phe	missense_variant	3/3	1	NM_018326.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00147

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000633

AC:

159

AN:

251058

Hom.:

AF XY:

0.000627

AC XY:

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00128

AC:

1869

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

880

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.000761

AC:

116

AN:

152338

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00147

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000913

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.00124

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

Oct 27, 2021

The c.352C>T (p.L118F) alteration is located in exon 3 (coding exon 2) of the GIMAP4 gene. This alteration results from a C to T substitution at nucleotide position 352, causing the leucine (L) at amino acid position 118 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.10

LIST_S2

Uncertain

0.89

D;D;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

4.1

H;.;.

MutationTaster

Benign

0.71

D;D

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.48

MVP

0.15

MPC

0.22

ClinPred

0.15

GERP RS

-2.7

Varity_R

0.86

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over