8-63064118-C-T

Position:

• chr8-63064118-C-T

Variant summary

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

The NM_000370.3(TTPA):​c.663+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 914,400 control chromosomes in the GnomAD database, including 118,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22261 hom., cov: 31)
  • Exomes 𝑓: 0.49 (96063 hom.)
• Consequence: TTPA NM_000370.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.139

Genes affected

TTPA (HGNC:12404): (alpha tocopherol transfer protein) This gene encodes a soluble protein that binds alpha-trocopherol, a form of vitamin E, with high selectivity and affinity. This protein plays an important role in regulating vitamin E levels in the body by transporting vitamin E between membrane vesicles and facilitating the secretion of vitamin E from hepatocytes to circulating lipoproteins. Mutations in this gene cause hereditary vitamin E deficiency (ataxia with vitamin E deficiency, AVED) and retinitis pigmentosa. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 8-63064118-C-T is Benign according to our data. Variant chr8-63064118-C-T is described in ClinVar as [Benign]. Clinvar id is 1259067.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTPA	NM_000370.3	c.663+88G>A		intron_variant		ENST00000260116.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTPA	ENST00000260116.5	c.663+88G>A		intron_variant		1	NM_000370.3	P1
TTPA	ENST00000521138.1	n.233-15515G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80980 AN: 151580 Hom.: 22231 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.494 AC: 377076 AN: 762702 Hom.: 96063 AF XY: 0.496 AC XY: 197042 AN XY: 397552

Gnomad4 AFR exome AF: 0.613

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.449

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.570

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.534 AC: 81057 AN: 151698 Hom.: 22261 Cov.: 31 AF XY: 0.542 AC XY: 40181 AN XY: 74084

Gnomad4 AFR AF: 0.618

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.515

Alfa AF: 0.496 Hom.: 2953

Bravo AF: 0.539

Asia WGS AF: 0.652 AC: 2260 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.6
DANN	Benign	0.34

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: rs4606052; hg19: chr8-63976677;