11-31463201-C-T

Variant names:

• chr11-31463201-C-T
• rs372148769
• NM_001304274.2:c.76G>A

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.76G>A​(p.Ala26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A26G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IMMP1L NM_001304274.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.90
• 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]

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=0.19163996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP1L	NM_001304274.2	c.76G>A	p.Ala26Thr	missense_variant	Exon 2 of 6	ENST00000532287.6	NP_001291203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP1L	ENST00000532287.6	c.76G>A	p.Ala26Thr	missense_variant	Exon 2 of 6	1	NM_001304274.2	ENSP00000435576.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457872 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725202

African (AFR) AF: 0.00 AC: 0 AN: 33284

American (AMR) AF: 0.00 AC: 0 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110218

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.55
DEOGEN2	Benign	0.012	T;.;T;T;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.82	L;.;L;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	1.1	N;N;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.68	T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.0	B;.;B;B;.
Vest4		0.37
MutPred		0.57		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.57
MPC		0.013
ClinPred		0.62	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.67
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs372148769; hg19: chr11-31484748;