2-86144494-T-C

Position:

• chr2-86144494-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006839.3(IMMT):​c.2051A>G​(p.Asp684Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.49

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMT	NM_006839.3	c.2051A>G	p.Asp684Gly	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.2051A>G	p.Asp684Gly	missense_variant	15/15	1	NM_006839.3	ENSP00000387262.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Apr 23, 2024

The c.2051A>G (p.D684G) alteration is located in exon 15 (coding exon 15) of the IMMT gene. This alteration results from a A to G substitution at nucleotide position 2051, causing the aspartic acid (D) at amino acid position 684 to be replaced by a glycine (G). 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	0.27
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T;.;T;.;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D
MetaSVM	Benign	-0.90	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-4.4	D;D;D;D;D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.021	D;D;D;D;D;.
Sift4G	Uncertain	0.011	D;D;D;D;D;D
Polyphen		1.0, 0.99	.;D;D;.;D;.
Vest4		0.72
MutPred		0.53		.;.;Gain of helix (P = 0.0034);.;.;.;
MVP		0.68
MPC		0.56
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.60
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-86371617;