rs2306986

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001386140.1(MTTP):c.294G>C(p.Glu98Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,613,268 control chromosomes in the GnomAD database, including 3,733 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 1009 hom., cov: 32)

Exomes 𝑓: 0.047 ( 2724 hom. )

Consequence

MTTP
NM_001386140.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.225

Publications

32 publications found

Variant links:

Genes affected

MTTP (HGNC:7467): (microsomal triglyceride transfer protein) MTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein. Protein disulfide isomerase (PDI) completes the heterodimeric microsomal triglyceride transfer protein, which has been shown to play a central role in lipoprotein assembly. Mutations in MTP can cause abetalipoproteinemia. [provided by RefSeq, Jul 2008]

MTTP Gene-Disease associations (from GenCC):

abetalipoproteinemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

MTTP links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001386140.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001547575).

BP6

Variant 4-99583418-G-C is Benign according to our data. Variant chr4-99583418-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 347021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386140.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTTP	NM_001386140.1	MANE Select	c.294G>C	p.Glu98Asp	missense	Exon 3 of 18	NP_001373069.1	P55157-1
MTTP	NM_000253.4		c.294G>C	p.Glu98Asp	missense	Exon 4 of 19	NP_000244.2	P55157-1
MTTP	NM_001300785.2		c.45G>C	p.Glu15Asp	missense	Exon 3 of 18	NP_001287714.2	E9PBP6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTTP	ENST00000265517.10	TSL:1 MANE Select	c.294G>C	p.Glu98Asp	missense	Exon 3 of 18	ENSP00000265517.5	P55157-1
MTTP	ENST00000422897.6	TSL:1	c.294G>C	p.Glu98Asp	missense	Exon 3 of 3	ENSP00000407350.2	P55157-2
MTTP	ENST00000457717.6	TSL:5	c.294G>C	p.Glu98Asp	missense	Exon 4 of 19	ENSP00000400821.1	P55157-1

Frequencies

GnomAD3 genomes

AF:

0.0856

AC:

13003

AN:

151976

Hom.:

1005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0641

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.0472

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0345

Gnomad OTH

AF:

0.0670

GnomAD2 exomes

AF:

0.0592

AC:

14750

AN:

249084

AF XY:

0.0546

show subpopulations

Gnomad AFR exome

AF:

0.194

Gnomad AMR exome

AF:

0.0542

Gnomad ASJ exome

AF:

0.0499

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.0210

Gnomad NFE exome

AF:

0.0343

Gnomad OTH exome

AF:

0.0442

GnomAD4 exome

AF:

0.0473

AC:

69149

AN:

1461174

Hom.:

2724

Cov.:

AF XY:

0.0466

AC XY:

33854

AN XY:

726872

show subpopulations

African (AFR)

AF:

0.197

AC:

6591

AN:

33444

American (AMR)

AF:

0.0533

AC:

2384

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

1309

AN:

26102

East Asian (EAS)

AF:

0.212

AC:

8408

AN:

39654

South Asian (SAS)

AF:

0.0408

AC:

3520

AN:

86212

European-Finnish (FIN)

AF:

0.0207

AC:

1099

AN:

53218

Middle Eastern (MID)

AF:

0.0609

AC:

351

AN:

5760

European-Non Finnish (NFE)

AF:

0.0378

AC:

42034

AN:

1111706

Other (OTH)

AF:

0.0572

AC:

3453

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

3410

6819

10229

13638

17048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1826

3652

5478

7304

9130

<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:

0.0856

AC:

13024

AN:

152094

Hom.:

1009

Cov.:

AF XY:

0.0837

AC XY:

6220

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.192

AC:

7957

AN:

41490

American (AMR)

AF:

0.0639

AC:

975

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3470

East Asian (EAS)

AF:

0.187

AC:

970

AN:

5174

South Asian (SAS)

AF:

0.0468

AC:

226

AN:

4826

European-Finnish (FIN)

AF:

0.0169

AC:

179

AN:

10604

Middle Eastern (MID)

AF:

0.0479

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0345

AC:

2347

AN:

67958

Other (OTH)

AF:

0.0720

AC:

152

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

547

1094

1640

2187

2734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0458

Hom.:

202

Bravo

AF:

0.0937

Asia WGS

AF:

0.109

AC:

376

AN:

3478

EpiCase

AF:

0.0362

EpiControl

AF:

0.0337

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Abetalipoproteinaemia (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PhyloP100

0.23

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.86

REVEL

Benign

0.026

Sift

Benign

0.12

Sift4G

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.29

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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