Genetic Variant NM_032549.4:c.335A>G (chr7-110886666-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_032549.4(IMMP2L):c.335A>G(p.Lys112Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,603,170 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 10 hom. )

Consequence

IMMP2L
NM_032549.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.668

Publications

2 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009037107).

BP6

Variant 7-110886666-T-C is Benign according to our data. Variant chr7-110886666-T-C is described in ClinVar as Benign. ClinVar VariationId is 3042696.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

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.335A>G	p.Lys112Arg	missense	Exon 5 of 6	NP_115938.1	Q96T52-1
IMMP2L	NM_001350961.2		c.419A>G	p.Lys140Arg	missense	Exon 7 of 8	NP_001337890.1
IMMP2L	NM_001244606.2		c.335A>G	p.Lys112Arg	missense	Exon 6 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.335A>G	p.Lys112Arg	missense	Exon 5 of 6	ENSP00000384966.2	Q96T52-1
IMMP2L	ENST00000331762.7	TSL:1	c.335A>G	p.Lys112Arg	missense	Exon 6 of 7	ENSP00000329553.3	Q96T52-1
IMMP2L	ENST00000452895.5	TSL:5	c.335A>G	p.Lys112Arg	missense	Exon 6 of 7	ENSP00000399353.1	Q96T52-1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00910

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00142

AC:

355

AN:

250594

AF XY:

0.00184

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.000752

AC:

1091

AN:

1450946

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

746

AN XY:

722678

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33184

American (AMR)

AF:

0.000358

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.0104

AC:

894

AN:

86004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000962

AC:

106

AN:

1102322

Other (OTH)

AF:

0.00113

AC:

AN:

60022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000420

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41558

American (AMR)

AF:

0.000196

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00911

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.000239

Hom.:

Bravo

AF:

0.000253

ExAC

AF:

0.00166

AC:

202

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

IMMP2L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.6

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

PhyloP100

0.67

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.22

REVEL

Benign

0.088

Sift

Benign

0.55

Sift4G

Benign

0.75

Polyphen

0.0020

Vest4

0.22

MVP

0.33

MPC

0.12

ClinPred

0.013

GERP RS

0.41

Varity_R

0.053

gMVP

0.34

Mutation Taster

=100/0

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