chr1-47794589-C-T

Position:

• chr1-47794589-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001194986.2(TRABD2B):​c.985G>A​(p.Ala329Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRABD2B NM_001194986.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.39

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRABD2B	NM_001194986.2	c.985G>A	p.Ala329Thr	missense_variant	4/7	ENST00000606738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRABD2B	ENST00000606738.3	c.985G>A	p.Ala329Thr	missense_variant	4/7	1	NM_001194986.2	P1
TRABD2B	ENST00000435576.2	n.326+6884G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.985G>A (p.A329T) alteration is located in exon 4 (coding exon 4) of the TRABD2B gene. This alteration results from a G to A substitution at nucleotide position 985, causing the alanine (A) at amino acid position 329 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.88	D
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.69	T
Sift4G	Uncertain	0.051	T
Vest4		0.92
MVP		0.23
MPC		1.9
GERP RS		4.6
Varity_R		0.15
gMVP		0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs1644720339; hg19: chr1-48260261;