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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTPAL	NM_001039199.3	MANE Select	c.*4846G>A	3_prime_UTR	Exon 5 of 5	NP_001034288.1	Q9BTX7
TTPAL	NM_024331.5		c.*4846G>A	3_prime_UTR	Exon 6 of 6	NP_077307.2	Q9BTX7
TTPAL	NM_001261839.2		c.*4846G>A	3_prime_UTR	Exon 5 of 5	NP_001248768.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TTPAL	ENST00000262605.9	TSL:1 MANE Select	c.*4846G>A	3_prime_UTR	Exon 5 of 5	ENSP00000262605.4	Q9BTX7
TTPAL	ENST00000372904.7	TSL:1	c.*4846G>A	3_prime_UTR	Exon 6 of 6	ENSP00000361995.3	Q9BTX7
TTPAL	ENST00000901712.1		c.*4846G>A	3_prime_UTR	Exon 5 of 5	ENSP00000571771.1

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 v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over