7-150627725-G-T

Variant names:

• chr7-150627725-G-T
• rs764186399
• NM_024711.6:c.873C>A

Variant summary

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

The NM_024711.6(GIMAP6):​c.873C>A​(p.Asp291Glu) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GIMAP6 NM_024711.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 1 publications found

Genes affected

GIMAP6 (HGNC:21918): (GTPase, IMAP family member 6) This gene encodes a member of the GTPases of immunity-associated proteins (GIMAP) family. GIMAP proteins contain GTP-binding and coiled-coil motifs, and may play roles in the regulation of cell survival. Decreased expression of this gene may play a role in non-small cell lung cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is found in a cluster with seven additional GIMAP genes on the long arm of chromosome 7. [provided by RefSeq, Sep 2011]

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=0.053946137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP6	NM_024711.6	c.873C>A	p.Asp291Glu	missense_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3
GIMAP6	NM_001244072.2	c.1083C>A	p.Asp361Glu	missense_variant	Exon 3 of 3		NP_001231001.1
GIMAP6	NM_001244071.2	c.*460C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001231000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIMAP6	ENST00000328902.9	c.873C>A	p.Asp291Glu	missense_variant	Exon 3 of 3	1	NM_024711.6	ENSP00000330374.5
GIMAP6	ENST00000618759.4	c.1083C>A	p.Asp361Glu	missense_variant	Exon 3 of 3	2		ENSP00000479580.1
GIMAP6	ENST00000493969.2	c.*460C>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000418304.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.6
DANN	Benign	0.65
DEOGEN2	Benign	0.0011	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.23	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;.
PhyloP100		1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.080	N;.
REVEL	Benign	0.17
Sift	Benign	0.45	T;.
Sift4G	Benign	0.98	T;T
Polyphen		0.0	B;.
Vest4		0.067
MutPred		0.14		Gain of loop (P = 0.1081);.;
MVP		0.13
MPC		0.12
ClinPred		0.059	T
GERP RS		0.68
Varity_R		0.033
gMVP		0.059
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: rs764186399; hg19: chr7-150324813;