11-75241072-C-T

Variant names:

• chr11-75241072-C-T
• rs1591862534
• NM_001195528.2:c.23C>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.23C>T​(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000877 in 1,140,358 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. 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. P8R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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]

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

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=0.09908724).

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.23C>T	p.Pro8Leu	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.23C>T	p.Pro8Leu	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	TPBGL-AS1	ENST00000530792.1	TSL:3	n.102G>A		non_coding_transcript_exon	Exon 1 of 4
	ENSG00000308808	ENST00000836519.1		n.176-1238G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.77e-7 AC: 1 AN: 1140358 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 552582

African (AFR) AF: 0.00 AC: 0 AN: 23030

American (AMR) AF: 0.00 AC: 0 AN: 10452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15334

East Asian (EAS) AF: 0.00 AC: 0 AN: 25214

South Asian (SAS) AF: 0.00 AC: 0 AN: 38326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3088

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 954600

Other (OTH) AF: 0.00 AC: 0 AN: 45368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0063	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.099	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.20
PrimateAI	Uncertain	0.77	T
Sift4G	Uncertain	0.043	D
Vest4		0.097
MVP		0.69
GERP RS		-0.76
PromoterAI		-0.028	Neutral
Varity_R		0.045
gMVP		0.31
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: rs1591862534; hg19: chr11-74952117;