Genetic Variant NM_130759.4:c.814A>G (chr7-150720818-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_130759.4(GIMAP1):c.814A>G(p.Arg272Gly) 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 benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GIMAP1
NM_130759.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.12

Variant links:

Genes affected

GIMAP1 (HGNC:23237): (GTPase, IMAP family member 1) 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. This gene is thought to be involved in the differentiation of T helper (Th) cells of the Th1 lineage, and the related mouse gene has been shown to be critical for the development of mature B and T lymphocytes. Read-through transcription exists between this gene and the downstream GIMAP5 (GTPase, IMAP family member 5) gene. [provided by RefSeq, Dec 2010]

GIMAP1 links:

GIMAP1-GIMAP5 (HGNC:51257): (GIMAP1-GIMAP5 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring GIMAP1 (GTPase, IMAP family member 1) and GIMAP5 (GTPase, IMAP family member 5) genes on chromosome 7. Alternative splicing results in multiple readthrough transcript variants, one of which encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2015]

GIMAP1-GIMAP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053805918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP1	NM_130759.4 link	c.814A>G	p.Arg272Gly	missense_variant	Exon 3 of 3	ENST00000307194.6	NP_570115.1	Q8WWP7A0A090N8Z4
GIMAP1-GIMAP5	NM_001199577.2 link	c.402+412A>G		intron_variant	Intron 3 of 5		NP_001186506.1	A0A087WTJ2
GIMAP1-GIMAP5	NM_001303630.2 link	c.18+1728A>G		intron_variant	Intron 2 of 4		NP_001290559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP1	ENST00000307194.6 link	c.814A>G	p.Arg272Gly	missense_variant	Exon 3 of 3	1	NM_130759.4	ENSP00000302833.5		Q8WWP7
GIMAP1-GIMAP5	ENST00000611999.4 link	c.402+412A>G		intron_variant	Intron 3 of 5	5		ENSP00000477920.1		A0A087WTJ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719326

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.814A>G (p.R272G) alteration is located in exon 3 (coding exon 2) of the GIMAP1 gene. This alteration results from a A to G substitution at nucleotide position 814, causing the arginine (R) at amino acid position 272 to be replaced by a glycine (G). 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

0.081

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.032

DANN

Benign

0.37

DEOGEN2

Benign

0.021

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.42

M_CAP

Benign

0.00072

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

PROVEAN

Benign

-0.24

REVEL

Benign

0.0040

Sift

Benign

0.40

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.058

MVP

0.043

MPC

0.87

ClinPred

0.11

GERP RS

-7.2

Varity_R

0.037

gMVP

0.87

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