11-75241335-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195528.2(TPBGL):​c.286C>A​(p.Leu96Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. L96V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32732204).

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>A	p.Leu96Met	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>A	p.Leu96Met	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+1208G>T		intron	N/A
	TPBGL-AS1	ENST00000530792.1	TSL:3	n.-162G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1204764 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 589390

African (AFR) AF: 0.00 AC: 0 AN: 23608

American (AMR) AF: 0.00 AC: 0 AN: 10868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17624

East Asian (EAS) AF: 0.00 AC: 0 AN: 26260

South Asian (SAS) AF: 0.00 AC: 0 AN: 52976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 991694

Other (OTH) AF: 0.00 AC: 0 AN: 48842

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Benign	0.70
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.33	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.0
PrimateAI	Pathogenic	0.91	D
Sift4G	Pathogenic	0.0	D
Vest4		0.48
MVP		0.17
GERP RS		3.4
Varity_R		0.11
gMVP		0.23
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;