rs2116542368

Variant names:

• chr7-150720439-A-C
• rs2116542368
• NM_130759.4:c.435A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-150720439-A-C
• chr7-150720439-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_130759.4(GIMAP1):​c.435A>C​(p.Lys145Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000493 in 1,420,732 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: GIMAP1 NM_130759.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.904
• Publications: 0 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: 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=0.14202508).

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.435A>C	p.Lys145Asn	missense	Exon 3 of 3	NP_570115.1	Q8WWP7
	GIMAP1-GIMAP5	NM_001199577.2		c.402+33A>C		intron	N/A	NP_001186506.1	A0A087WTJ2
	GIMAP1-GIMAP5	NM_001303630.2		c.18+1349A>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.435A>C	p.Lys145Asn	missense	Exon 3 of 3	ENSP00000302833.5	Q8WWP7
	GIMAP1-GIMAP5	ENST00000611999.4	TSL:5	c.402+33A>C		intron	N/A	ENSP00000477920.1	A0A087WTJ2
	GIMAP1	ENST00000867917.1		c.435A>C	p.Lys145Asn	missense	Exon 2 of 2	ENSP00000537976.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000493 AC: 7 AN: 1420732 Hom.: 0 Cov.: 31 AF XY: 0.00000570 AC XY: 4 AN XY: 701544

African (AFR) AF: 0.00 AC: 0 AN: 32658

American (AMR) AF: 0.00 AC: 0 AN: 41334

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22912

East Asian (EAS) AF: 0.00 AC: 0 AN: 39360

South Asian (SAS) AF: 0.00 AC: 0 AN: 78790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1089988

Other (OTH) AF: 0.0000171 AC: 1 AN: 58592

GnomAD4 genome Cov.: 33

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	0.33
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.96
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L
PhyloP100		-0.90
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.064
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.81	P
Vest4		0.11
MutPred		0.53		Loss of methylation at K145 (P = 0.0071)
MVP		0.12
MPC		1.4
ClinPred		0.16	T
GERP RS		-0.45
Varity_R		0.18
gMVP		0.57
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2116542368; hg19: chr7-150417527;