7-110663631-G-T

Variant names:

• chr7-110663631-G-T
• NM_032549.4:c.499C>A

Variant summary

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

The NM_032549.4(IMMP2L):​c.499C>A​(p.Arg167Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IMMP2L NM_032549.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58

Genes affected

IMMP2L (HGNC:14598): (inner mitochondrial membrane peptidase subunit 2) This gene encodes a protein involved in processing the signal peptide sequences used to direct mitochondrial proteins to the mitochondria. The encoded protein resides in the mitochondria and is one of the necessary proteins for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Two variants that encode the same protein have been described for this gene. [provided by RefSeq, Sep 2011]

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=0.24948335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP2L	NM_032549.4	c.499C>A	p.Arg167Ser	missense_variant	Exon 6 of 6	ENST00000405709.7	NP_115938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP2L	ENST00000405709.7	c.499C>A	p.Arg167Ser	missense_variant	Exon 6 of 6	1	NM_032549.4	ENSP00000384966.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.499C>A (p.R167S) alteration is located in exon 6 (coding exon 5) of the IMMP2L gene. This alteration results from a C to A substitution at nucleotide position 499, causing the arginine (R) at amino acid position 167 to be replaced by a serine (S). 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	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	.;.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M;M;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N;N;N;D
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.80	P;P;P;.
Vest4		0.47
MutPred		0.30		Gain of phosphorylation at R167 (P = 0.0292);Gain of phosphorylation at R167 (P = 0.0292);Gain of phosphorylation at R167 (P = 0.0292);.;
MVP		0.57
MPC		0.36
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.49
gMVP		0.78

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: chr7-110303687;