rs1303629218

Variant names:

• chr11-75241267-T-A
• NM_001195528.2:c.218T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-75241267-T-A
• chr11-75241267-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001195528.2(TPBGL):​c.218T>A​(p.Leu73Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000826 in 1,210,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L73P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPBGL	NM_001195528.2	c.218T>A	p.Leu73Gln	missense_variant	Exon 1 of 1	ENST00000562197.3	NP_001182457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPBGL	ENST00000562197.3	c.218T>A	p.Leu73Gln	missense_variant	Exon 1 of 1	6	NM_001195528.2	ENSP00000474988.1
TPBGL-AS1	ENST00000530792.1	n.-94A>T		upstream_gene_variant		3
TPBGL-AS1	ENST00000603012.1	n.-220A>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.26e-7 AC: 1 AN: 1210818 Hom.: 0 Cov.: 30 AF XY: 0.00000169 AC XY: 1 AN XY: 592316

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Benign	0.89
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.56	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.52	D
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Pathogenic	0.95	D
Sift4G	Uncertain	0.0020	D
Vest4		0.49
MVP		0.51
GERP RS		4.3
Varity_R		0.48
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-74952312;