Genetic Variant IMMP2L:p.Asp99Asn (chr7-110963510-C-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032549.4(IMMP2L):c.295G>A(p.Asp99Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,598,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

IMMP2L
NM_032549.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

Publications

0 publications found

Variant links:

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]

IMMP2L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.937

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IMMP2L	NM_032549.4	MANE Select	c.295G>A	p.Asp99Asn	missense	Exon 4 of 6	NP_115938.1	Q96T52-1
IMMP2L	NM_001350961.2		c.379G>A	p.Asp127Asn	missense	Exon 6 of 8	NP_001337890.1
IMMP2L	NM_001244606.2		c.295G>A	p.Asp99Asn	missense	Exon 5 of 7	NP_001231535.1	Q96T52-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IMMP2L	ENST00000405709.7	TSL:1 MANE Select	c.295G>A	p.Asp99Asn	missense	Exon 4 of 6	ENSP00000384966.2	Q96T52-1
IMMP2L	ENST00000331762.7	TSL:1	c.295G>A	p.Asp99Asn	missense	Exon 5 of 7	ENSP00000329553.3	Q96T52-1
IMMP2L	ENST00000452895.5	TSL:5	c.295G>A	p.Asp99Asn	missense	Exon 5 of 7	ENSP00000399353.1	Q96T52-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000406

AC:

AN:

246458

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000968

AC:

AN:

1446984

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32888

American (AMR)

AF:

0.00

AC:

AN:

43972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25844

East Asian (EAS)

AF:

0.00

AC:

AN:

39304

South Asian (SAS)

AF:

0.00

AC:

AN:

85214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1101050

Other (OTH)

AF:

0.00

AC:

AN:

59760

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000777

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

EpiCase

AF:

0.0000551

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.78

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.94

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.4

PhyloP100

6.0

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.7

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.96

MVP

0.78

MPC

0.62

ClinPred

0.99

GERP RS

5.7

Varity_R

0.83

gMVP

0.71

Mutation Taster

=57/43

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over