chr1-47775197-T-C

Variant names:

• chr1-47775197-T-C
• rs1644428157
• NM_001194986.2:c.1322A>G

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.1322A>G​(p.Asn441Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,239,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TRABD2B NM_001194986.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• 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=0.13559401).

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.1322A>G	p.Asn441Ser	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.1322A>G	p.Asn441Ser	missense	Exon 6 of 7	ENSP00000476820.1	A6NFA1
	TRABD2B	ENST00000878673.1		c.1427A>G	p.Asn476Ser	missense	Exon 7 of 8	ENSP00000548732.1
	TRABD2B	ENST00000878672.1		c.1175A>G	p.Asn392Ser	missense	Exon 5 of 6	ENSP00000548731.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1086876 Hom.: 0 Cov.: 31 AF XY: 0.00000194 AC XY: 1 AN XY: 514164

African (AFR) AF: 0.00 AC: 0 AN: 23124

American (AMR) AF: 0.00 AC: 0 AN: 8942

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14524

East Asian (EAS) AF: 0.00 AC: 0 AN: 26768

South Asian (SAS) AF: 0.00 AC: 0 AN: 21784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2946

European-Non Finnish (NFE) AF: 0.00000325 AC: 3 AN: 922796

Other (OTH) AF: 0.00 AC: 0 AN: 44004

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.047
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.53
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.14	T
MutationAssessor	Benign	0.82	L
PhyloP100		3.1
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.55	T
Vest4		0.14
MVP		0.23
MPC		0.69
GERP RS		4.6
Varity_R		0.097
gMVP		0.16
Mutation Taster		=78/22	polymorphism

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: rs1644428157; hg19: chr1-48240869;