chr1-47775377-G-T

Variant names:

• chr1-47775377-G-T
• rs1235986922
• NM_001194986.2:c.1142C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001194986.2(TRABD2B):​c.1142C>A​(p.Thr381Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict 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. T381I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRABD2B NM_001194986.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21684587).

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.1142C>A	p.Thr381Asn	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.1142C>A	p.Thr381Asn	missense	Exon 6 of 7	ENSP00000476820.1	A6NFA1
	TRABD2B	ENST00000878673.1		c.1247C>A	p.Thr416Asn	missense	Exon 7 of 8	ENSP00000548732.1
	TRABD2B	ENST00000878672.1		c.995C>A	p.Thr332Asn	missense	Exon 5 of 6	ENSP00000548731.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1085502 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 513278

African (AFR) AF: 0.00 AC: 0 AN: 23126

American (AMR) AF: 0.00 AC: 0 AN: 8638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14470

East Asian (EAS) AF: 0.00 AC: 0 AN: 26612

South Asian (SAS) AF: 0.00 AC: 0 AN: 21060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4210

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 921704

Other (OTH) AF: 0.00 AC: 0 AN: 43970

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0053	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.22	T
MutationAssessor	Benign	0.69	N
PhyloP100		6.3
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.36	T
Vest4		0.11
MVP		0.13
MPC		1.7
GERP RS		5.1
Varity_R		0.066
gMVP		0.22
Mutation Taster		=94/6	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: rs1235986922; hg19: chr1-48241049;