7-150628056-T-G

Variant names:

• chr7-150628056-T-G
• rs747155481
• NM_024711.6:c.542A>C

Variant summary

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

The NM_024711.6(GIMAP6):​c.542A>C​(p.Asn181Thr) 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. 15/22 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. N181K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GIMAP6 NM_024711.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 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: 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=0.08346176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024711.6. 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
	GIMAP6	NM_024711.6	MANE Select	c.542A>C	p.Asn181Thr	missense	Exon 3 of 3	NP_078987.3
	GIMAP6	NM_001244072.2		c.752A>C	p.Asn251Thr	missense	Exon 3 of 3	NP_001231001.1	B4DH95
	GIMAP6	NM_001244071.2		c.*129A>C		3_prime_UTR	Exon 3 of 3	NP_001231000.1	Q6P9H5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GIMAP6	ENST00000328902.9	TSL:1 MANE Select	c.542A>C	p.Asn181Thr	missense	Exon 3 of 3	ENSP00000330374.5	Q6P9H5-1
	GIMAP6	ENST00000618759.4	TSL:2	c.752A>C	p.Asn251Thr	missense	Exon 3 of 3	ENSP00000479580.1	B4DH95
	GIMAP6	ENST00000971115.1		c.752A>C	p.Asn251Thr	missense	Exon 3 of 3	ENSP00000641174.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.022
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.091	B
Vest4		0.066
MutPred		0.43		Gain of catalytic residue at N181 (P = 0.0041)
MVP		0.14
MPC		0.16
ClinPred		0.14	T
GERP RS		1.9
Varity_R		0.16
gMVP		0.49
Mutation Taster		=99/1	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: rs747155481; hg19: chr7-150325144;