Genetic Variant IMMT:p.Pro124Ser (chr2-86173701-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006839.3(IMMT):c.370C>T(p.Pro124Ser) variant causes a missense change. The variant allele was found at a frequency of 0.337 in 1,598,506 control chromosomes in the GnomAD database, including 96,177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 7133 hom., cov: 32)

Exomes 𝑓: 0.34 ( 89044 hom. )

Consequence

IMMT
NM_006839.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.14

Publications

41 publications found

Variant links:

Genes affected

IMMT (HGNC:6047): (inner membrane mitochondrial protein) Enables RNA binding activity. Involved in cristae formation. Located in mitochondrial inner membrane. Part of MICOS complex. [provided by Alliance of Genome Resources, Apr 2022]

IMMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.4006786E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006839.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IMMT	NM_006839.3	MANE Select	c.370C>T	p.Pro124Ser	missense	Exon 4 of 15	NP_006830.2
IMMT	NM_001100169.2		c.370C>T	p.Pro124Ser	missense	Exon 4 of 15	NP_001093639.1
IMMT	NM_001400086.1		c.370C>T	p.Pro124Ser	missense	Exon 4 of 15	NP_001387015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IMMT	ENST00000410111.8	TSL:1 MANE Select	c.370C>T	p.Pro124Ser	missense	Exon 4 of 15	ENSP00000387262.3
IMMT	ENST00000442664.6	TSL:1	c.370C>T	p.Pro124Ser	missense	Exon 4 of 15	ENSP00000407788.2
IMMT	ENST00000449247.6	TSL:1	c.370C>T	p.Pro124Ser	missense	Exon 4 of 15	ENSP00000396899.2

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42308

AN:

151994

Hom.:

7129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0792

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.441

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.319

GnomAD2 exomes

AF:

0.364

AC:

89785

AN:

246872

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.0698

Gnomad AMR exome

AF:

0.443

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.513

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.343

AC:

496621

AN:

1446394

Hom.:

89044

Cov.:

AF XY:

0.347

AC XY:

249730

AN XY:

720206

show subpopulations

African (AFR)

AF:

0.0650

AC:

2170

AN:

33410

American (AMR)

AF:

0.436

AC:

19350

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

10313

AN:

25998

East Asian (EAS)

AF:

0.491

AC:

19423

AN:

39548

South Asian (SAS)

AF:

0.433

AC:

37085

AN:

85562

European-Finnish (FIN)

AF:

0.339

AC:

18066

AN:

53306

Middle Eastern (MID)

AF:

0.393

AC:

2241

AN:

5708

European-Non Finnish (NFE)

AF:

0.334

AC:

367291

AN:

1098644

Other (OTH)

AF:

0.345

AC:

20682

AN:

59864

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

14486

28973

43459

57946

72432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11856

23712

35568

47424

59280

<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:

0.278

AC:

42319

AN:

152112

Hom.:

7133

Cov.:

AF XY:

0.285

AC XY:

21158

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0790

AC:

3277

AN:

41502

American (AMR)

AF:

0.363

AC:

5549

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1366

AN:

3468

East Asian (EAS)

AF:

0.500

AC:

2590

AN:

5176

South Asian (SAS)

AF:

0.442

AC:

2132

AN:

4824

European-Finnish (FIN)

AF:

0.353

AC:

3734

AN:

10576

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22707

AN:

67982

Other (OTH)

AF:

0.318

AC:

670

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1469

2937

4406

5874

7343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.312

Hom.:

16936

Bravo

AF:

0.275

TwinsUK

AF:

0.333

AC:

1235

ALSPAC

AF:

0.330

AC:

1271

ESP6500AA

AF:

0.0905

AC:

331

ESP6500EA

AF:

0.337

AC:

2750

ExAC

AF:

0.358

AC:

43296

Asia WGS

AF:

0.431

AC:

1497

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.73

MetaRNN

Benign

0.00084

MetaSVM

Benign

-0.90

PhyloP100

6.1

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.12

Sift

Uncertain

0.014

Sift4G

Benign

0.15

Polyphen

0.94

Vest4

0.39

MPC

0.45

ClinPred

0.025

GERP RS

3.4

PromoterAI

0.0028

Neutral

(source)

Varity_R

0.086

gMVP

0.48

Mutation Taster

=91/9

polymorphism (auto)

(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