rs3805335

Positions:

• chr4-99586478-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MTTP	NM_001386140.1	c.393+2961C>T		intron_variant		ENST00000265517.10	NP_001373069.1
MTTP	NM_000253.4	c.393+2961C>T		intron_variant			NP_000244.2
MTTP	NM_001300785.2	c.144+2961C>T		intron_variant			NP_001287714.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTTP	ENST00000265517.10	c.393+2961C>T		intron_variant		1	NM_001386140.1	ENSP00000265517.5
MTTP	ENST00000457717.6	c.393+2961C>T		intron_variant		5		ENSP00000400821.1
MTTP	ENST00000511045.6	c.144+2961C>T		intron_variant		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

Gnomad4 AFR AF: 0.00716

Gnomad4 AMR AF: 0.0731

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0985

Gnomad4 SAS AF: 0.00457

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000839

Gnomad4 OTH AF: 0.0214

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

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: rs3805335; hg19: chr4-100507635;