Genetic Variant NM_024711.6:c.875T>C (chr7-150627723-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024711.6(GIMAP6):c.875T>C(p.Leu292Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GIMAP6
NM_024711.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.109

Publications

0 publications found

Variant links:

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]

GIMAP6 links:

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ACMG classification

Classification was made for transcript

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=0.105754375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIMAP6	NM_024711.6 link	c.875T>C	p.Leu292Pro	missense_variant	Exon 3 of 3	ENST00000328902.9	NP_078987.3	Q6P9H5-1A0A090N7V4
GIMAP6	NM_001244072.2 link	c.1085T>C	p.Leu362Pro	missense_variant	Exon 3 of 3		NP_001231001.1	Q6P9H5B4DH95
GIMAP6	NM_001244071.2 link	c.*462T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001231000.1	Q6P9H5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GIMAP6	ENST00000328902.9 link	c.875T>C	p.Leu292Pro	missense_variant	Exon 3 of 3	1	NM_024711.6	ENSP00000330374.5	Q6P9H5-1
GIMAP6	ENST00000618759.4 link	c.1085T>C	p.Leu362Pro	missense_variant	Exon 3 of 3	2		ENSP00000479580.1	B4DH95
GIMAP6	ENST00000493969.2 link	c.*462T>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000418304.1	Q6P9H5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111436

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.875T>C (p.L292P) alteration is located in exon 3 (coding exon 2) of the GIMAP6 gene. This alteration results from a T to C substitution at nucleotide position 875, causing the leucine (L) at amino acid position 292 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

0.093

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.

PhyloP100

0.11

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.028

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.015

D;D

Polyphen

0.88

P;.

Vest4

0.060

MutPred

0.18

Loss of stability (P = 0.0174);.;

MVP

0.26

MPC

0.54

ClinPred

0.31

GERP RS

1.2

Varity_R

0.22

gMVP

0.28

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over