chr2-86144303-C-A

Position:

• chr2-86144303-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006839.3(IMMT):​c.2242G>T​(p.Val748Leu) 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. 12/20 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)
• Consequence: IMMT NM_006839.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33967698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMT	NM_006839.3	c.2242G>T	p.Val748Leu	missense_variant	15/15	ENST00000410111.8	NP_006830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMMT	ENST00000410111.8	c.2242G>T	p.Val748Leu	missense_variant	15/15	1	NM_006839.3	ENSP00000387262.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249164 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.2242G>T (p.V748L) alteration is located in exon 15 (coding exon 15) of the IMMT gene. This alteration results from a G to T substitution at nucleotide position 2242, causing the valine (V) at amino acid position 748 to be replaced by a leucine (L). 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	0.23
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T;.;T;.;T;.
Eigen	Benign	-0.040
Eigen_PC	Benign	0.084
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.4	N;N;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.052	T;T;T;T;T;.
Sift4G	Uncertain	0.056	T;D;D;D;D;T
Polyphen		0.099, 0.033	.;B;B;.;B;.
Vest4		0.44
MutPred		0.59		.;.;Gain of helix (P = 0.027);.;.;.;
MVP		0.39
MPC		0.11
ClinPred		0.36	T
GERP RS		4.4
Varity_R		0.16
gMVP		0.53

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

Other links and lift over

dbSNP: rs183939253; hg19: chr2-86371426;