NM_000370.3:c.663+88G>C

Variant names:

• chr8-63064118-C-G
• rs4606052
• NM_000370.3:c.663+88G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000370.3(TTPA):​c.663+88G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTPA NM_000370.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139
• Publications: 9 publications found

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]

TTPA Gene-Disease associations (from GenCC):

• familial isolated deficiency of vitamin E

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000370.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTPA	NM_000370.3	MANE Select	c.663+88G>C		intron	N/A	NP_000361.1	P49638
	TTPA	NM_001413418.1		c.780+88G>C		intron	N/A	NP_001400347.1
	TTPA	NM_001413416.1		c.663+88G>C		intron	N/A	NP_001400345.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTPA	ENST00000260116.5	TSL:1 MANE Select	c.663+88G>C		intron	N/A	ENSP00000260116.4	P49638
	TTPA	ENST00000878696.1		c.780+88G>C		intron	N/A	ENSP00000548755.1
	TTPA	ENST00000878697.1		c.552+1786G>C		intron	N/A	ENSP00000548756.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 764888 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 398632

African (AFR) AF: 0.00 AC: 0 AN: 19506

American (AMR) AF: 0.00 AC: 0 AN: 34120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20794

East Asian (EAS) AF: 0.00 AC: 0 AN: 32724

South Asian (SAS) AF: 0.00 AC: 0 AN: 63658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 506012

Other (OTH) AF: 0.00 AC: 0 AN: 36900

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 2953

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		0.14

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: rs4606052; hg19: chr8-63976677;