7-150720518-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130759.4(GIMAP1):c.514C>T(p.Arg172Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 1,448,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: GIMAP1 NM_130759.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.176

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-GIMAP5 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26160735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIMAP1	NM_130759.4	c.514C>T	p.Arg172Trp	missense_variant	3/3	ENST00000307194.6
GIMAP1-GIMAP5	NM_001199577.2	c.402+112C>T		intron_variant
GIMAP1-GIMAP5	NM_001303630.2	c.18+1428C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIMAP1	ENST00000307194.6	c.514C>T	p.Arg172Trp	missense_variant	3/3	1	NM_130759.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000690 AC: 10 AN: 1448932 Hom.: 0 Cov.: 31 AF XY: 0.00000973 AC XY: 7 AN XY: 719636

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000723

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Feb 13, 2024

The c.514C>T (p.R172W) alteration is located in exon 3 (coding exon 2) of the GIMAP1 gene. This alteration results from a C to T substitution at nucleotide position 514, causing the arginine (R) at amino acid position 172 to be replaced by a tryptophan (W). 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	0.15
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.077
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	1.0	N
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.12
Sift	Benign	0.050	D
Sift4G	Benign	0.094	T
Polyphen		1.0	D
Vest4		0.21
MutPred		0.49		Loss of disorder (P = 0.0184);
MVP		0.43
MPC		1.7
ClinPred		0.85	D
GERP RS		1.7
Varity_R		0.29
gMVP		0.84

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

Other links and lift over

dbSNP: rs1417844598; hg19: chr7-150417606; COSMIC: COSV100212349; COSMIC: COSV100212349;