dbSNP rs1983: TTPAL:c.*4846G>A (chr20-44494387-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001039199.3(TTPAL):c.*4846G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 152,548 control chromosomes in the GnomAD database, including 13,235 homozygotes. 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: 𝑓 0.38 ( 13171 hom., cov: 31)

Exomes 𝑓: 0.46 ( 64 hom. )

Consequence

TTPAL
NM_001039199.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.607

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTPAL	NM_001039199.3 link	c.*4846G>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000262605.9	NP_001034288.1	Q9BTX7B2RA57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTPAL	ENST00000262605.9 link	c.*4846G>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_001039199.3	ENSP00000262605.4		Q9BTX7
TTPAL	ENST00000372904.7 link	c.*4846G>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000361995.3		Q9BTX7

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57232

AN:

151854

Hom.:

13172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.0357

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.394

GnomAD4 exome

AF:

0.464

AC:

267

AN:

576

Hom.:

Cov.:

AF XY:

0.488

AC XY:

165

AN XY:

338

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.449

AC:

AN:

136

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.462

AC:

196

AN:

424

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.600

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.377

AC:

57230

AN:

151972

Hom.:

13171

Cov.:

AF XY:

0.371

AC XY:

27562

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.149

AC:

6193

AN:

41480

American (AMR)

AF:

0.348

AC:

5302

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1495

AN:

3466

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5176

South Asian (SAS)

AF:

0.334

AC:

1607

AN:

4814

European-Finnish (FIN)

AF:

0.454

AC:

4788

AN:

10546

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36187

AN:

67926

Other (OTH)

AF:

0.389

AC:

821

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1575

3151

4726

6302

7877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.473

Hom.:

33565

Bravo

AF:

0.359

Asia WGS

AF:

0.163

AC:

571

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over