chr7-110886634-C-A

Variant names:

• chr7-110886634-C-A
• NM_032549.4:c.367G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032549.4(IMMP2L):​c.367G>T​(p.Asp123Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.62
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032549.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMP2L	NM_032549.4	MANE Select	c.367G>T	p.Asp123Tyr	missense	Exon 5 of 6	NP_115938.1	Q96T52-1
	IMMP2L	NM_001350961.2		c.451G>T	p.Asp151Tyr	missense	Exon 7 of 8	NP_001337890.1
	IMMP2L	NM_001244606.2		c.367G>T	p.Asp123Tyr	missense	Exon 6 of 7	NP_001231535.1	Q96T52-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMP2L	ENST00000405709.7	TSL:1 MANE Select	c.367G>T	p.Asp123Tyr	missense	Exon 5 of 6	ENSP00000384966.2	Q96T52-1
	IMMP2L	ENST00000331762.7	TSL:1	c.367G>T	p.Asp123Tyr	missense	Exon 6 of 7	ENSP00000329553.3	Q96T52-1
	IMMP2L	ENST00000452895.5	TSL:5	c.367G>T	p.Asp123Tyr	missense	Exon 6 of 7	ENSP00000399353.1	Q96T52-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	4.7	H
PhyloP100		7.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-8.4	D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.99
MutPred		0.77		Loss of disorder (P = 0.012)
MVP		0.75
MPC		0.70
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.97
gMVP		0.90
Mutation Taster		=29/71	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr7-110526690;