rs1057613

Variant names:

• chr4-99583828-G-A
• rs1057613
• ENST00000422897.6:c.*248G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422897.6(MTTP):​c.*248G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 506,028 control chromosomes in the GnomAD database, including 81,833 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 0.60 (30340 hom., cov: 32)
  • Exomes 𝑓: 0.52 (51493 hom.)
• Consequence: MTTP ENST00000422897.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 13 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.393+311G>A		intron_variant	Intron 3 of 17	ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.393+311G>A		intron_variant	Intron 4 of 18		NP_000244.2
MTTP	NM_001300785.2	c.144+311G>A		intron_variant	Intron 3 of 17		NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000422897.6	c.*248G>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000407350.2
MTTP	ENST00000265517.10	c.393+311G>A		intron_variant	Intron 3 of 17	1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.393+311G>A		intron_variant	Intron 4 of 18	5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.144+311G>A		intron_variant	Intron 3 of 17	2		ENSP00000427679.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90416 AN: 151812 Hom.: 30294 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.520 AC: 183982 AN: 354098 Hom.: 51493 Cov.: 2 AF XY: 0.524 AC XY: 97229 AN XY: 185408

African (AFR) AF: 0.904 AC: 9212 AN: 10194

American (AMR) AF: 0.411 AC: 5144 AN: 12524

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 8065 AN: 11504

East Asian (EAS) AF: 0.839 AC: 21645 AN: 25804

South Asian (SAS) AF: 0.617 AC: 19004 AN: 30820

European-Finnish (FIN) AF: 0.310 AC: 6647 AN: 21428

Middle Eastern (MID) AF: 0.622 AC: 997 AN: 1604

European-Non Finnish (NFE) AF: 0.466 AC: 101949 AN: 218868

Other (OTH) AF: 0.530 AC: 11319 AN: 21352

GnomAD4 genome AF: 0.596 AC: 90503 AN: 151930 Hom.: 30340 Cov.: 32 AF XY: 0.589 AC XY: 43755 AN XY: 74234

African (AFR) AF: 0.897 AC: 37258 AN: 41528

American (AMR) AF: 0.472 AC: 7186 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2440 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3997 AN: 5172

South Asian (SAS) AF: 0.614 AC: 2955 AN: 4812

European-Finnish (FIN) AF: 0.305 AC: 3212 AN: 10524

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31442 AN: 67878

Other (OTH) AF: 0.605 AC: 1272 AN: 2104

Alfa AF: 0.503 Hom.: 10603

Bravo AF: 0.617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.40
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1057613; hg19: chr4-100504985;