7-150474030-T-C

Position:

• chr7-150474030-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_175571.4(GIMAP8):​c.701T>C​(p.Leu234Pro) 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. 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: 31)
• Consequence: GIMAP8 NM_175571.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.98

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

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=0.029731572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIMAP8	NM_175571.4	c.701T>C	p.Leu234Pro	missense_variant	4/5	ENST00000307271.4	NP_783161.1
GIMAP8	XM_005249950.5	c.701T>C	p.Leu234Pro	missense_variant	5/6		XP_005250007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIMAP8	ENST00000307271.4	c.701T>C	p.Leu234Pro	missense_variant	4/5	1	NM_175571.4	ENSP00000305107.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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 26, 2024

The c.701T>C (p.L234P) alteration is located in exon 4 (coding exon 3) of the GIMAP8 gene. This alteration results from a T to C substitution at nucleotide position 701, causing the leucine (L) at amino acid position 234 to be replaced by a proline (P). 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	0.058
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.18
DANN	Benign	0.29
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.00081	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.028
Sift	Benign	0.15	T
Sift4G	Benign	0.077	T
Polyphen		0.0010	B
Vest4		0.055
MutPred		0.17		Gain of helix (P = 0.0425);
MVP		0.14
MPC		0.24
ClinPred		0.068	T
GERP RS		-7.9
Varity_R		0.054
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150171118;