rs890394501

Variant summary

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

The NM_001195528.2(TPBGL):​c.568G>A​(p.Ala190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 1,162,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A190P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

TPBGL
NM_001195528.2 missense

Scores

1
1
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.201
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]

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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=0.11963403).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPBGLNM_001195528.2 linkc.568G>A p.Ala190Thr missense_variant Exon 1 of 1 ENST00000562197.3 NP_001182457.1 P0DKB5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPBGLENST00000562197.3 linkc.568G>A p.Ala190Thr missense_variant Exon 1 of 1 6 NM_001195528.2 ENSP00000474988.1 P0DKB5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000172
AC:
2
AN:
1162894
Hom.:
0
Cov.:
30
AF XY:
0.00000175
AC XY:
1
AN XY:
571396
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000105
Gnomad4 OTH exome
AF:
0.0000224
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.86
DEOGEN2
Benign
0.0075
T
FATHMM_MKL
Benign
0.062
N
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.19
D
MetaRNN
Benign
0.12
T
MutationAssessor
Benign
0.85
L
PrimateAI
Pathogenic
0.91
D
Sift4G
Benign
0.34
T
Vest4
0.080
MVP
0.20
GERP RS
1.9
Varity_R
0.024
gMVP
0.19

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.

Other links and lift over

dbSNP: rs890394501; hg19: chr11-74952662; API