7-150627747-C-G

Variant names:

• chr7-150627747-C-G
• NM_024711.6:c.851G>C

Variant summary

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

The NM_024711.6(GIMAP6):​c.851G>C​(p.Arg284Thr) 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: 33)
• Consequence: GIMAP6 NM_024711.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.888

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

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=0.059903353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP6	NM_024711.6	c.851G>C	p.Arg284Thr	missense_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3
GIMAP6	NM_001244072.2	c.1061G>C	p.Arg354Thr	missense_variant	Exon 3 of 3		NP_001231001.1
GIMAP6	NM_001244071.2	c.*438G>C		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.851G>C	p.Arg284Thr	missense_variant	Exon 3 of 3	1	NM_024711.6	ENSP00000330374.5
GIMAP6	ENST00000618759.4	c.1061G>C	p.Arg354Thr	missense_variant	Exon 3 of 3	2		ENSP00000479580.1
GIMAP6	ENST00000493969	c.*438G>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000418304.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.851G>C (p.R284T) alteration is located in exon 3 (coding exon 2) of the GIMAP6 gene. This alteration results from a G to C substitution at nucleotide position 851, causing the arginine (R) at amino acid position 284 to be replaced by a threonine (T). 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	0.17
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	1.6
DANN	Benign	0.70
DEOGEN2	Benign	0.0055	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.025
Sift	Uncertain	0.0090	D;.
Sift4G	Uncertain	0.018	D;D
Polyphen		0.022	B;.
Vest4		0.11
MutPred		0.22		Loss of loop (P = 0.1258);.;
MVP		0.061
MPC		0.20
ClinPred		0.051	T
GERP RS		-7.0
Varity_R		0.051
gMVP		0.54

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: chr7-150324835;