chr11-75241473-C-T

Variant names:

• chr11-75241473-C-T
• rs1240839261
• NM_001195528.2:c.424C>T

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.424C>T​(p.Pro142Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,106,332 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.176
• 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:):

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=0.207851).

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.424C>T	p.Pro142Ser	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.424C>T	p.Pro142Ser	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+1070G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 2758 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: 0.00000994 AC: 11 AN: 1106332 Hom.: 0 Cov.: 30 AF XY: 0.00000751 AC XY: 4 AN XY: 532832

African (AFR) AF: 0.000136 AC: 3 AN: 22016

American (AMR) AF: 0.00 AC: 0 AN: 7868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13472

East Asian (EAS) AF: 0.00 AC: 0 AN: 23608

South Asian (SAS) AF: 0.00 AC: 0 AN: 35050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2872

European-Non Finnish (NFE) AF: 0.00000321 AC: 3 AN: 934830

Other (OTH) AF: 0.000116 AC: 5 AN: 43150

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0040	T
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.21	T
MutationAssessor	Benign	0.25	N
PhyloP100		0.18
PrimateAI	Pathogenic	0.91	D
Sift4G	Benign	1.0	T
Vest4		0.17
MVP		0.48
GERP RS		3.4
Varity_R		0.12
gMVP		0.18
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: rs1240839261; hg19: chr11-74952518;