Variant 4-99564087-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000457717.6(MTTP):c.-252G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,533,796 control chromosomes in the GnomAD database, including 17,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1982 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15259 hom. )

Consequence

MTTP
ENST00000457717.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0710

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 links:

TRMT10A (HGNC:28403): (tRNA methyltransferase 10A) This gene encodes a protein that belongs to the tRNA (Guanine-1)-methyltransferase family. A similar gene in yeast modifies several different tRNA species. Mutations in this gene are associated with microcephaly, short stature, and impaired glucose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

TRMT10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-99564087-G-C is Benign according to our data. Variant chr4-99564087-G-C is described in ClinVar as [Benign]. Clinvar id is 347008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-99564087-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT10A	NM_001134665.3 linkuse as main transcript			upstream_gene_variant		ENST00000394876.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT10A	ENST00000394876.7 linkuse as main transcript			upstream_gene_variant		1	NM_001134665.3	P1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24069

AN:

151894

Hom.:

1983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.155

AC:

20195

AN:

130520

Hom.:

1793

AF XY:

0.163

AC XY:

11618

AN XY:

71234

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.0936

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.135

Gnomad SAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.143

AC:

197838

AN:

1381782

Hom.:

15259

Cov.:

AF XY:

0.147

AC XY:

100290

AN XY:

681838

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.0968

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.262

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.149

GnomAD4 genome

AF:

0.158

AC:

24077

AN:

152014

Hom.:

1982

Cov.:

AF XY:

0.159

AC XY:

11787

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.278

Gnomad4 FIN

AF:

0.136

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.141

Hom.:

290

Bravo

AF:

0.155

Asia WGS

AF:

0.236

AC:

817

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Abetalipoproteinaemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.2

DANN

Benign

0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over