Variant chr20-44480320-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001039199.3(TTPAL):c.321A>C(p.Arg107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TTPAL
NM_001039199.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.323

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=0.096705794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTPAL	NM_001039199.3 linkuse as main transcript	c.321A>C	p.Arg107Ser	missense_variant	2/5	ENST00000262605.9	NP_001034288.1	Q9BTX7B2RA57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTPAL	ENST00000262605.9 linkuse as main transcript	c.321A>C	p.Arg107Ser	missense_variant	2/5	1	NM_001039199.3	ENSP00000262605.4	Q9BTX7
TTPAL	ENST00000372904.7 linkuse as main transcript	c.321A>C	p.Arg107Ser	missense_variant	3/6	1		ENSP00000361995.3	Q9BTX7
TTPAL	ENST00000456317.1 linkuse as main transcript	c.321A>C	p.Arg107Ser	missense_variant	2/5	2		ENSP00000412720.1	Q5QPC2
TTPAL	ENST00000372906.2 linkuse as main transcript	c.321A>C	p.Arg107Ser	missense_variant	2/3	3		ENSP00000361997.2	A6PVK2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152142

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251432

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Dec 11, 2023

The c.321A>C (p.R107S) alteration is located in exon 3 (coding exon 1) of the TTPAL gene. This alteration results from a A to C substitution at nucleotide position 321, causing the arginine (R) at amino acid position 107 to be replaced by a serine (S). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.23

CADD

Benign

7.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0099

T;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.58

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.066

MetaRNN

Benign

0.097

T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

0.34

N;N;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.26

B;B;.;.

Vest4

0.35

MutPred

0.45

Loss of solvent accessibility (P = 0.1322);Loss of solvent accessibility (P = 0.1322);Loss of solvent accessibility (P = 0.1322);Loss of solvent accessibility (P = 0.1322);

MVP

0.44

MPC

0.70

ClinPred

0.22

GERP RS

-4.8

Varity_R

0.19

gMVP

0.63

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