rs3805335

Variant names:

• chr4-99586478-C-T
• rs3805335
• NM_001386140.1:c.393+2961C>T

Variant summary

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

The NM_001386140.1(MTTP):​c.393+2961C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 151,994 control chromosomes in the GnomAD database, including 106 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 0.014 (106 hom., cov: 32)
• Consequence: MTTP NM_001386140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.393+2961C>T		intron_variant	Intron 3 of 17	ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.393+2961C>T		intron_variant	Intron 4 of 18		NP_000244.2
MTTP	NM_001300785.2	c.144+2961C>T		intron_variant	Intron 3 of 17		NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.393+2961C>T		intron_variant	Intron 3 of 17	1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.393+2961C>T		intron_variant	Intron 4 of 18	5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.144+2961C>T		intron_variant	Intron 3 of 17	2		ENSP00000427679.2

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2046 AN: 151876 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00718

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.00436

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000839

Gnomad OTH AF: 0.0212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0135 AC: 2052 AN: 151994 Hom.: 106 Cov.: 32 AF XY: 0.0141 AC XY: 1051 AN XY: 74286

African (AFR) AF: 0.00716 AC: 297 AN: 41482

American (AMR) AF: 0.0731 AC: 1114 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.0985 AC: 509 AN: 5168

South Asian (SAS) AF: 0.00457 AC: 22 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000839 AC: 57 AN: 67940

Other (OTH) AF: 0.0214 AC: 45 AN: 2102

Alfa AF: 0.0210 Hom.: 45

Bravo AF: 0.0222

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.65
PhyloP100		0.24
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: rs3805335; hg19: chr4-100507635;