Genetic Variant IMMP1L:p.His105Asp (chr11-31456268-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001304274.2(IMMP1L):c.313C>G(p.His105Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000126 in 1,591,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IMMP1L
NM_001304274.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Publications

0 publications found

Variant links:

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]

IMMP1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2687773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMMP1L	NM_001304274.2 link	c.313C>G	p.His105Asp	missense_variant	Exon 4 of 6	ENST00000532287.6	NP_001291203.1	Q96LU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMMP1L	ENST00000532287.6 link	c.313C>G	p.His105Asp	missense_variant	Exon 4 of 6	1	NM_001304274.2	ENSP00000435576.1		Q96LU5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439136

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33002

American (AMR)

AF:

0.00

AC:

AN:

43952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25700

East Asian (EAS)

AF:

0.00

AC:

AN:

39356

South Asian (SAS)

AF:

0.00

AC:

AN:

83198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4590

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097172

Other (OTH)

AF:

0.0000168

AC:

AN:

59442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41380

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.313C>G (p.H105D) alteration is located in exon 5 (coding exon 3) of the IMMP1L gene. This alteration results from a C to G substitution at nucleotide position 313, causing the histidine (H) at amino acid position 105 to be replaced by an aspartic acid (D). 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

0.18

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.083

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

.;D;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.7

L;L;.

PhyloP100

7.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.16

T;T;D

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.65

MutPred

0.43

Gain of phosphorylation at Y107 (P = 0.0775);Gain of phosphorylation at Y107 (P = 0.0775);Gain of phosphorylation at Y107 (P = 0.0775);

MVP

0.33

MPC

0.016

ClinPred

0.89

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.66

Mutation Taster

=67/33

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over