chr11-75241362-C-A

Variant names:

• chr11-75241362-C-A
• NM_001195528.2:c.313C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001195528.2(TPBGL):​c.313C>A​(p.His105Asn) 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. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TPBGL NM_001195528.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06531274).
• BP6: Variant 11-75241362-C-A is Benign according to our data. Variant chr11-75241362-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2534698.Status of the report is criteria_provided_single_submitter, 1 stars.

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.313C>A	p.His105Asn	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.313C>A	p.His105Asn	missense	Exon 1 of 1	ENSP00000474988.1	P0DKB5
	ENSG00000308808	ENST00000836519.1		n.175+1181G>T		intron	N/A
	TPBGL-AS1	ENST00000530792.1	TSL:3	n.-189G>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: 1223722 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 600108

African (AFR) AF: 0.00 AC: 0 AN: 24058

American (AMR) AF: 0.00 AC: 0 AN: 14226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19056

East Asian (EAS) AF: 0.00 AC: 0 AN: 26236

South Asian (SAS) AF: 0.00 AC: 0 AN: 57888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3924

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 998792

Other (OTH) AF: 0.00 AC: 0 AN: 49528

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.036
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.76
DEOGEN2	Benign	0.0053	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.065	T
MutationAssessor	Benign	-0.64	N
PhyloP100		-0.31
PrimateAI	Pathogenic	0.90	D
Sift4G	Benign	1.0	T
Vest4		0.074
MVP		0.42
GERP RS		1.9
Varity_R		0.12
gMVP		0.11
Mutation Taster		=89/11	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

hg19: chr11-74952407;