Variant chr2-86144303-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006839.3(IMMT):c.2242G>A(p.Val748Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

IMMT
NM_006839.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Variant links:

Genes affected

IMMT (HGNC:6047): (inner membrane mitochondrial protein) Enables RNA binding activity. Involved in cristae formation. Located in mitochondrial inner membrane. Part of MICOS complex. [provided by Alliance of Genome Resources, Apr 2022]

IMMT links:

IMMT (HGNC:):

IMMT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.031011492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMT	NM_006839.3 linkuse as main transcript	c.2242G>A	p.Val748Ile	missense_variant	15/15	ENST00000410111.8	NP_006830.2	Q16891-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMMT	ENST00000410111.8 linkuse as main transcript	c.2242G>A	p.Val748Ile	missense_variant	15/15	1	NM_006839.3	ENSP00000387262.3		Q16891-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000165

AC:

AN:

249164

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000113

AC:

165

AN:

1461692

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000241

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2022

The c.2242G>A (p.V748I) alteration is located in exon 15 (coding exon 15) of the IMMT gene. This alteration results from a G to A substitution at nucleotide position 2242, causing the valine (V) at amino acid position 748 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;T;.;T;.

Eigen

Benign

-0.099

Eigen_PC

Benign

0.048

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T;T;T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.031

T;T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.47

N;N;N;N;N;.

REVEL

Benign

0.082

Sift

Benign

0.30

T;T;T;T;T;.

Sift4G

Benign

0.076

T;D;T;T;D;T

Polyphen

0.011, 0.0030

.;B;B;.;B;.

Vest4

0.16

MVP

0.34

MPC

0.090

ClinPred

0.042

GERP RS

4.4

Varity_R

0.067

gMVP

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over