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).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GIMAP6	NM_024711.6	MANE Select	c.875T>C	p.Leu292Pro	missense	Exon 3 of 3	NP_078987.3
GIMAP6	NM_001244072.2		c.1085T>C	p.Leu362Pro	missense	Exon 3 of 3	NP_001231001.1	B4DH95
GIMAP6	NM_001244071.2		c.*462T>C		3_prime_UTR	Exon 3 of 3	NP_001231000.1	Q6P9H5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GIMAP6	ENST00000328902.9	TSL:1 MANE Select	c.875T>C	p.Leu292Pro	missense	Exon 3 of 3	ENSP00000330374.5	Q6P9H5-1
GIMAP6	ENST00000618759.4	TSL:2	c.1085T>C	p.Leu362Pro	missense	Exon 3 of 3	ENSP00000479580.1	B4DH95
GIMAP6	ENST00000971115.1		c.1085T>C	p.Leu362Pro	missense	Exon 3 of 3	ENSP00000641174.1

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.34

M_CAP

Benign

0.0023

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.11

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.028

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.015

Polyphen

0.88

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over