NM_001194986.2:c.1307G>A

Variant names:

• chr1-47775212-C-T
• rs1294384012
• NM_001194986.2:c.1307G>A

Variant summary

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

The NM_001194986.2(TRABD2B):​c.1307G>A​(p.Arg436Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000367 in 1,088,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: TRABD2B NM_001194986.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

TRABD2B (HGNC:44200): (TraB domain containing 2B) Enables Wnt-protein binding activity and metalloendopeptidase activity. Involved in several processes, including negative regulation of Wnt signaling pathway; positive regulation of protein oxidation; and positive regulation of protein-containing complex assembly. Is integral component of organelle membrane and integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.40352994).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001194986.2. 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
	TRABD2B	NM_001194986.2	MANE Select	c.1307G>A	p.Arg436Gln	missense	Exon 6 of 7	NP_001181915.1	A6NFA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRABD2B	ENST00000606738.3	TSL:1 MANE Select	c.1307G>A	p.Arg436Gln	missense	Exon 6 of 7	ENSP00000476820.1	A6NFA1
	TRABD2B	ENST00000878673.1		c.1412G>A	p.Arg471Gln	missense	Exon 7 of 8	ENSP00000548732.1
	TRABD2B	ENST00000878672.1		c.1160G>A	p.Arg387Gln	missense	Exon 5 of 6	ENSP00000548731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000367 AC: 4 AN: 1088970 Hom.: 0 Cov.: 31 AF XY: 0.00000388 AC XY: 2 AN XY: 515440

African (AFR) AF: 0.00 AC: 0 AN: 23158

American (AMR) AF: 0.00 AC: 0 AN: 9086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14558

East Asian (EAS) AF: 0.00 AC: 0 AN: 26796

South Asian (SAS) AF: 0.00 AC: 0 AN: 22446

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2980

European-Non Finnish (NFE) AF: 0.00000433 AC: 4 AN: 923698

Other (OTH) AF: 0.00 AC: 0 AN: 44094

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.40	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.7
PrimateAI	Uncertain	0.62	T
Sift4G	Uncertain	0.048	D
Vest4		0.36
MVP		0.23
MPC		2.0
GERP RS		5.7
Varity_R		0.13
gMVP		0.41
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1294384012; hg19: chr1-48240884;