11-75241335-C-G

Variant names:

• chr11-75241335-C-G
• rs868712288
• NM_001195528.2:c.286C>G

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.286C>G​(p.Leu96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.00
• Publications: 0 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:):

TPBGL-AS1 (HGNC:55506): (TPBGL antisense RNA 1)

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=0.20677486).

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.286C>G	p.Leu96Val	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.286C>G	p.Leu96Val	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+1208G>C		intron	N/A
	TPBGL-AS1	ENST00000530792.1	TSL:3	n.-162G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150874 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73678

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41304

American (AMR) AF: 0.00 AC: 0 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67558

Other (OTH) AF: 0.00 AC: 0 AN: 2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Benign	0.43
DEOGEN2	Benign	0.069	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.21	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.0
PrimateAI	Pathogenic	0.90	D
Sift4G	Pathogenic	0.0	D
Vest4		0.30
MVP		0.23
GERP RS		3.4
Varity_R		0.083
gMVP		0.22
Mutation Taster		=98/2	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: rs868712288; hg19: chr11-74952380;