11-75241543-A-T

Variant names:

• chr11-75241543-A-T
• rs1334834693
• NM_001195528.2:c.494A>T

Variant summary

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

The NM_001195528.2(TPBGL):​c.494A>T​(p.Asp165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000027 in 1,111,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D165A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28811955).

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.494A>T	p.Asp165Val	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.494A>T	p.Asp165Val	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+1000T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000270 AC: 3 AN: 1111134 Hom.: 0 Cov.: 30 AF XY: 0.00000185 AC XY: 1 AN XY: 541170

African (AFR) AF: 0.00 AC: 0 AN: 21636

American (AMR) AF: 0.00 AC: 0 AN: 10382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13852

East Asian (EAS) AF: 0.00 AC: 0 AN: 20118

South Asian (SAS) AF: 0.00 AC: 0 AN: 44876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2848

European-Non Finnish (NFE) AF: 0.00000322 AC: 3 AN: 931546

Other (OTH) AF: 0.00 AC: 0 AN: 42362

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.29	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.10
PrimateAI	Pathogenic	0.90	D
Sift4G	Uncertain	0.033	D
Vest4		0.25
MVP		0.51
GERP RS		4.1
Varity_R		0.29
gMVP		0.46
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: rs1334834693; hg19: chr11-74952588;