NM_130759.4:c.752T>C

Variant names:

• chr7-150720756-T-C
• rs1046572739
• NM_130759.4:c.752T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130759.4(GIMAP1):​c.752T>C​(p.Val251Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 1,567,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: GIMAP1 NM_130759.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.17
• Publications: 1 publications found

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: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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048806727).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130759.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP1	NM_130759.4	MANE Select	c.752T>C	p.Val251Ala	missense	Exon 3 of 3	NP_570115.1	Q8WWP7
	GIMAP1-GIMAP5	NM_001199577.2		c.402+350T>C		intron	N/A	NP_001186506.1	A0A087WTJ2
	GIMAP1-GIMAP5	NM_001303630.2		c.18+1666T>C		intron	N/A	NP_001290559.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP1	ENST00000307194.6	TSL:1 MANE Select	c.752T>C	p.Val251Ala	missense	Exon 3 of 3	ENSP00000302833.5	Q8WWP7
	GIMAP1-GIMAP5	ENST00000611999.4	TSL:5	c.402+350T>C		intron	N/A	ENSP00000477920.1	A0A087WTJ2
	GIMAP1	ENST00000867917.1		c.752T>C	p.Val251Ala	missense	Exon 2 of 2	ENSP00000537976.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000606 AC: 1 AN: 165036 AF XY: 0.00

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1414952 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 700130

African (AFR) AF: 0.000124 AC: 4 AN: 32288

American (AMR) AF: 0.00 AC: 0 AN: 37418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25376

East Asian (EAS) AF: 0.00 AC: 0 AN: 36776

South Asian (SAS) AF: 0.00 AC: 0 AN: 81568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088772

Other (OTH) AF: 0.00 AC: 0 AN: 58578

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74316

African (AFR) AF: 0.0000966 AC: 4 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.034
DANN	Benign	0.62
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.2
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.036
Sift	Benign	0.23	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.019
MutPred		0.46		Gain of disorder (P = 0.0344)
MVP		0.12
MPC		0.82
ClinPred		0.014	T
GERP RS		-1.1
Varity_R		0.16
gMVP		0.87
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1046572739; hg19: chr7-150417844;