11-75241617-G-A

Variant names:

• chr11-75241617-G-A
• rs890394501
• NM_001195528.2:c.568G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 1 publications found

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]

ENSG00000308808 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11963403).

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.568G>A	p.Ala190Thr	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.568G>A	p.Ala190Thr	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+926C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 45002 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000172 AC: 2 AN: 1162894 Hom.: 0 Cov.: 30 AF XY: 0.00000175 AC XY: 1 AN XY: 571396

African (AFR) AF: 0.00 AC: 0 AN: 22288

American (AMR) AF: 0.00 AC: 0 AN: 14752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16728

East Asian (EAS) AF: 0.00 AC: 0 AN: 20906

South Asian (SAS) AF: 0.00 AC: 0 AN: 57494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3080

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 956478

Other (OTH) AF: 0.0000224 AC: 1 AN: 44688

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.20
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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs890394501; hg19: chr11-74952662;