Variant 22-50198345-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001320485.2(TRABD):c.957C>T(p.Thr319=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,563,474 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 2 hom. )

Consequence

TRABD
NM_001320485.2 splice_region, synonymous

Scores

Splicing: ADA: 0.00005623

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.100

Variant links:

Genes affected

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

TRABD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 22-50198345-C-T is Benign according to our data. Variant chr22-50198345-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3181730.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.1 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRABD	NM_001320485.2 linkuse as main transcript	c.957C>T	p.Thr319=	splice_region_variant, synonymous_variant	10/10	ENST00000380909.9	NP_001307414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRABD	ENST00000380909.9 linkuse as main transcript	c.957C>T	p.Thr319=	splice_region_variant, synonymous_variant	10/10	5	NM_001320485.2	ENSP00000370295	P1	Q9H4I3-1

Frequencies

GnomAD3 genomes

AF:

0.000415

AC:

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000530

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000477

AC:

AN:

190856

Hom.:

AF XY:

0.000538

AC XY:

AN XY:

105926

show subpopulations

Gnomad AFR exome

AF:

0.000322

Gnomad AMR exome

AF:

0.000727

Gnomad ASJ exome

AF:

0.000147

Gnomad EAS exome

AF:

0.0000629

Gnomad SAS exome

AF:

0.000251

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000583

Gnomad OTH exome

AF:

0.00173

GnomAD4 exome

AF:

0.000352

AC:

497

AN:

1411384

Hom.:

Cov.:

AF XY:

0.000398

AC XY:

278

AN XY:

698436

show subpopulations

Gnomad4 AFR exome

AF:

0.000310

Gnomad4 AMR exome

AF:

0.000710

Gnomad4 ASJ exome

AF:

0.0000846

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.000361

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000316

Gnomad4 OTH exome

AF:

0.000808

GnomAD4 genome

AF:

0.000414

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.1

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.036

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over