Variant 20-44480429-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000262605.9(TTPAL):c.430G>A(p.Val144Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,602,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

TTPAL
ENST00000262605.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

TTPAL (HGNC:16114): (alpha tocopherol transfer protein like) Predicted to enable phosphatidylinositol bisphosphate binding activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

TTPAL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.122048885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTPAL	NM_001039199.3 linkuse as main transcript	c.430G>A	p.Val144Ile	missense_variant	2/5	ENST00000262605.9	NP_001034288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TTPAL	ENST00000262605.9 linkuse as main transcript	c.430G>A	p.Val144Ile	missense_variant	2/5	1	NM_001039199.3	ENSP00000262605	P1
TTPAL	ENST00000372904.7 linkuse as main transcript	c.430G>A	p.Val144Ile	missense_variant	3/6	1		ENSP00000361995	P1
TTPAL	ENST00000456317.1 linkuse as main transcript	c.430G>A	p.Val144Ile	missense_variant	2/5	2		ENSP00000412720
TTPAL	ENST00000372906.2 linkuse as main transcript	c.430G>A	p.Val144Ile	missense_variant	2/3	3		ENSP00000361997

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000248

AC:

AN:

241768

Hom.:

AF XY:

0.0000381

AC XY:

AN XY:

131086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000459

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000469

AC:

AN:

1450514

Hom.:

Cov.:

AF XY:

0.0000514

AC XY:

AN XY:

720042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000570

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.430G>A (p.V144I) alteration is located in exon 3 (coding exon 1) of the TTPAL gene. This alteration results from a G to A substitution at nucleotide position 430, causing the valine (V) at amino acid position 144 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.044

T;T;.;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

.;T;T;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

-0.39

N;N;.;.

MutationTaster

Benign

0.83

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.27

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.91

T;T;T;T

Sift4G

Benign

0.85

T;T;T;T

Polyphen

0.058

B;B;.;.

Vest4

0.15

MVP

0.20

MPC

0.31

ClinPred

0.033

GERP RS

1.4

Varity_R

0.028

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over