GeneBe

chr8-63066054-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_000370.3(TTPA):​c.402A>C​(p.Arg134Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R134R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TTPA
NM_000370.3 synonymous

Scores

3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.332

Publications

0 publications found
Variant links:
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: Myriad Women's Health, Labcorp Genetics (formerly Invitae), Orphanet, G2P

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000370.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP7
Synonymous conserved (PhyloP=0.332 with no splicing effect.

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TTPA
NM_000370.3
MANE Select
c.402A>Cp.Arg134Arg
synonymous
Exon 3 of 5NP_000361.1P49638
TTPA
NM_001413418.1
c.519A>Cp.Arg173Arg
synonymous
Exon 4 of 6NP_001400347.1
TTPA
NM_001413416.1
c.402A>Cp.Arg134Arg
synonymous
Exon 3 of 5NP_001400345.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TTPA
ENST00000260116.5
TSL:1 MANE Select
c.402A>Cp.Arg134Arg
synonymous
Exon 3 of 5ENSP00000260116.4P49638
TTPA
ENST00000878696.1
c.519A>Cp.Arg173Arg
synonymous
Exon 4 of 6ENSP00000548755.1
TTPA
ENST00000878697.1
c.402A>Cp.Arg134Arg
synonymous
Exon 3 of 4ENSP00000548756.1

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151388
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461730
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727160
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33472
American (AMR)
AF:
0.00
AC:
0
AN:
44684
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26128
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39682
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53402
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00000360
AC:
4
AN:
1111952
Other (OTH)
AF:
0.00
AC:
0
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151388
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
73886
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41080
American (AMR)
AF:
0.00
AC:
0
AN:
15132
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5126
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4782
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10540
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67966
Other (OTH)
AF:
0.00
AC:
0
AN:
2068
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
CADD
Benign
8.5
DANN
Benign
0.68
PhyloP100
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

Other links and lift over

dbSNP: rs373811993;
hg19: chr8-63978613;
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