chr7-150466972-C-T

Variant names:

• chr7-150466972-C-T
• rs903724377
• NM_175571.4:c.274C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_175571.4(GIMAP8):​c.274C>T​(p.Pro92Ser) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P92A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIMAP8 NM_175571.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 0 publications found

Genes affected

GIMAP8 (HGNC:21792): (GTPase, IMAP family member 8) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37069136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175571.4. 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
	GIMAP8	NM_175571.4	MANE Select	c.274C>T	p.Pro92Ser	missense	Exon 2 of 5	NP_783161.1	Q8ND71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP8	ENST00000307271.4	TSL:1 MANE Select	c.274C>T	p.Pro92Ser	missense	Exon 2 of 5	ENSP00000305107.3	Q8ND71
	GIMAP8	ENST00000901634.1		c.274C>T	p.Pro92Ser	missense	Exon 3 of 6	ENSP00000571693.1
	GIMAP8	ENST00000901635.1		c.274C>T	p.Pro92Ser	missense	Exon 2 of 5	ENSP00000571694.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.024
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.055
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.27
MutPred		0.61		Gain of loop (P = 0.069)
MVP		0.47
MPC		0.52
ClinPred		0.83	D
GERP RS		2.3
Varity_R		0.079
gMVP		0.24
Mutation Taster		=89/11	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: rs903724377; hg19: chr7-150164060; COSMIC: COSV56230725;