Genetic Variant TPBGL:p.Gly135Ser (chr11-75241452-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001195528.2(TPBGL):c.403G>A(p.Gly135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,274,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

TPBGL
NM_001195528.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0290

Publications

1 publications found

Variant links:

Genes affected

TPBGL (HGNC:44159): (trophoblast glycoprotein like) Predicted to be involved in negative regulation of canonical Wnt signaling pathway. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TPBGL links:

ENSG00000308808 (HGNC:):

ENSG00000308808 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015360475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195528.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPBGL	NM_001195528.2	MANE Select	c.403G>A	p.Gly135Ser	missense	Exon 1 of 1	NP_001182457.1	P0DKB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPBGL	ENST00000562197.3	TSL:6 MANE Select	c.403G>A	p.Gly135Ser	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+1091C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000412

AC:

AN:

150382

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.000579

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000845

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000592

AC:

AN:

6760

AF XY:

0.000671

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000937

Gnomad OTH exome

AF:

0.00610

GnomAD4 exome

AF:

0.000418

AC:

470

AN:

1124360

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

225

AN XY:

543196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22434

American (AMR)

AF:

0.00

AC:

AN:

8550

Ashkenazi Jewish (ASJ)

AF:

0.000835

AC:

AN:

14364

East Asian (EAS)

AF:

0.0000406

AC:

AN:

24642

South Asian (SAS)

AF:

0.000108

AC:

AN:

37162

European-Finnish (FIN)

AF:

0.000206

AC:

AN:

24302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2994

European-Non Finnish (NFE)

AF:

0.000462

AC:

437

AN:

945668

Other (OTH)

AF:

0.000249

AC:

AN:

44244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000412

AC:

AN:

150488

Hom.:

Cov.:

AF XY:

0.000354

AC XY:

AN XY:

73504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41308

American (AMR)

AF:

0.0000660

AC:

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.000579

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

9946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000845

AC:

AN:

67432

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000276

ExAC

AF:

0.000209

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0043

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.19

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.015

MutationAssessor

Benign

-0.12

PhyloP100

-0.029

PrimateAI

Pathogenic

0.87

Sift4G

Benign

0.84

Vest4

0.10

MVP

0.39

GERP RS

1.1

Varity_R

0.056

gMVP

0.24

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