22-50193067-G-T

Position:

• chr22-50193067-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320485.2(TRABD):​c.7G>T​(p.Gly3Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,393,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRABD NM_001320485.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

Genes affected

TRABD (HGNC:28805): (TraB domain containing)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.122624785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRABD	NM_001320485.2	c.7G>T	p.Gly3Trp	missense_variant	2/10	ENST00000380909.9	NP_001307414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRABD	ENST00000380909.9	c.7G>T	p.Gly3Trp	missense_variant	2/10	5	NM_001320485.2	ENSP00000370295	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1393572 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 687698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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 22, 2023

The c.7G>T (p.G3W) alteration is located in exon 2 (coding exon 1) of the TRABD gene. This alteration results from a G to T substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 to be replaced by a tryptophan (W). 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	Benign	0.12
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;T;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.53	.;.;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;N;N;.
MutationTaster	Benign	0.84	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		0.98	D;D;D;.
Vest4		0.41
MutPred		0.083		Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);
MVP		0.043
MPC		0.66
ClinPred		0.50	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.068
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50631496;