Genetic Variant GIMAP4:p.Ser7Asn (chr7-150569921-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018326.3(GIMAP4):c.20G>A(p.Ser7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GIMAP4
NM_018326.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.254

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09727487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP4	NM_018326.3 link	c.20G>A	p.Ser7Asn	missense_variant	Exon 2 of 3	ENST00000255945.4	NP_060796.1	Q9NUV9A0A090N7X0
GIMAP4	NM_001363532.2 link	c.20G>A	p.Ser7Asn	missense_variant	Exon 2 of 3		NP_001350461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP4	ENST00000255945.4 link	c.20G>A	p.Ser7Asn	missense_variant	Exon 2 of 3	1	NM_018326.3	ENSP00000255945.2		Q9NUV9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1428148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711720

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32740

American (AMR)

AF:

0.00

AC:

AN:

44298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25610

East Asian (EAS)

AF:

0.00

AC:

AN:

38888

South Asian (SAS)

AF:

0.00

AC:

AN:

85678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1083880

Other (OTH)

AF:

0.00

AC:

AN:

58964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 11, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.20G>A (p.S7N) alteration is located in exon 2 (coding exon 1) of the GIMAP4 gene. This alteration results from a G to A substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by an asparagine (N). 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

0.093

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.9

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.025

T;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.40

T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.097

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.;.

PhyloP100

0.25

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.20

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.045

D;T;D

Sift4G

Benign

0.37

T;T;T

Polyphen

0.42

B;B;.

Vest4

0.13

MutPred

0.19

Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);

MVP

0.28

MPC

0.056

ClinPred

0.23

GERP RS

2.4

Varity_R

0.070

gMVP

0.38

Mutation Taster

=99/1

polymorphism

(source)

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

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7-150569921-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over