2-86144764-C-G

Position:

• chr2-86144764-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006839.3(IMMT):​c.1781G>C​(p.Ser594Thr) 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. 14/20 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: 1.21

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07700607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMMT	NM_006839.3	c.1781G>C	p.Ser594Thr	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.1781G>C	p.Ser594Thr	missense_variant	15/15	1	NM_006839.3	ENSP00000387262.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Oct 16, 2023

The c.1781G>C (p.S594T) alteration is located in exon 15 (coding exon 15) of the IMMT gene. This alteration results from a G to C substitution at nucleotide position 1781, causing the serine (S) at amino acid position 594 to be replaced by a threonine (T). 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	0.071
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.016	T;.;T;.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.70	T;T;T;T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.077	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.070
Sift	Benign	0.28	T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;.;B
Vest4		0.045
MutPred		0.51		.;.;Loss of disorder (P = 0.1132);.;.;
MVP		0.24
MPC		0.10
ClinPred		0.097	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-86371887;