chr11-31432522-C-A

Variant names:

• chr11-31432522-C-A
• rs1195587340
• NM_001304274.2:c.479G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001304274.2(IMMP1L):​c.479G>T​(p.Gly160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: IMMP1L NM_001304274.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 0 publications found

Genes affected

IMMP1L (HGNC:26317): (inner mitochondrial membrane peptidase subunit 1) The mitochondrial inner membrane peptidase (IMP) complex generates mature, active proteins in the mitochondrial intermembrane space by proteolytically removing the mitochondrial targeting presequence of nuclear-encoded proteins. IMP1 and IMP2 (IMMP2L; MIM 605977) are the catalytic subunits of the IMP complex (Burri et al., 2005 [PubMed 15814844]).[supplied by OMIM, Sep 2008]

DNAJC24 (HGNC:26979): (DnaJ heat shock protein family (Hsp40) member C24) Diphthamide is a unique posttranslationally modified histidine found only in translation elongation factor-2 (EEF2; MIM 130610). This modification is conserved from archaebacteria to humans and serves as the target for ADP-ribosylation and inactivation of EEF2 by diphtheria toxin (DT) and Pseudomonas exotoxin A. DPH4 is 1 of several enzymes involved in synthesis of diphthamide in EEF2 (Liu et al., 2004 [PubMed 15485916]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16888317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304274.2. 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
	IMMP1L	NM_001304274.2	MANE Select	c.479G>T	p.Gly160Val	missense	Exon 6 of 6	NP_001291203.1	Q96LU5
	DNAJC24	NM_181706.5	MANE Select	c.*2121C>A		3_prime_UTR	Exon 5 of 5	NP_859057.4
	IMMP1L	NM_144981.3		c.479G>T	p.Gly160Val	missense	Exon 7 of 7	NP_659418.1	Q96LU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMMP1L	ENST00000532287.6	TSL:1 MANE Select	c.479G>T	p.Gly160Val	missense	Exon 6 of 6	ENSP00000435576.1	Q96LU5
	DNAJC24	ENST00000465995.6	TSL:1 MANE Select	c.*2121C>A		3_prime_UTR	Exon 5 of 5	ENSP00000417548.1	Q6P3W2-1
	IMMP1L	ENST00000278200.5	TSL:2	c.479G>T	p.Gly160Val	missense	Exon 7 of 7	ENSP00000278200.1	Q96LU5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

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	Benign	0.11
BayesDel_addAF	Benign	0.0052	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.092
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.048	D
Polyphen		0.082	B
Vest4		0.49
MutPred		0.39		Loss of disorder (P = 0.0267)
MVP		0.34
MPC		0.014
ClinPred		0.81	D
GERP RS		4.7
Varity_R		0.17
gMVP		0.63
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs1195587340; hg19: chr11-31454069;