4-99564087-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.0710

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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			upstream_gene_variant		ENST00000394876.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24069 AN: 151894 Hom.: 1983 Cov.: 32

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

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.: 31 AF XY: 0.147 AC XY: 100290 AN XY: 681838

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.: 32 AF XY: 0.159 AC XY: 11787 AN XY: 74290

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:3

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

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

Abetalipoproteinaemia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

Other links and lift over

dbSNP: rs11944749; hg19: chr4-100485244;