Variant 18-80044233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024805.3(RBFA):c.598G>A(p.Ala200Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000692 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00073 ( 0 hom. )

Consequence

RBFA
NM_024805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

RBFA (HGNC:26120): (ribosome binding factor A) Predicted to be involved in rRNA processing. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

RBFA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32179904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFA	NM_024805.3 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	6/7	ENST00000306735.10	NP_079081.2
RBFA	NM_001171967.2 linkuse as main transcript	c.513G>A	p.Ser171=	synonymous_variant	5/6		NP_001165438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFA	ENST00000306735.10 linkuse as main transcript	c.598G>A	p.Ala200Thr	missense_variant	6/7	1	NM_024805.3	ENSP00000305696	P1	Q8N0V3-1
RBFA	ENST00000262197.7 linkuse as main transcript	c.513G>A	p.Ser171=	synonymous_variant	5/6	1		ENSP00000262197		Q8N0V3-2
RBFA	ENST00000593019.1 linkuse as main transcript	n.940G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000676

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000326

AC:

AN:

251494

Hom.:

AF XY:

0.000353

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000668

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000732

AC:

1070

AN:

1461756

Hom.:

Cov.:

AF XY:

0.000675

AC XY:

491

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000933

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000309

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000302

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000346

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.598G>A (p.A200T) alteration is located in exon 6 (coding exon 6) of the RBFA gene. This alteration results from a G to A substitution at nucleotide position 598, causing the alanine (A) at amino acid position 200 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

0.46

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.61

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.65

MVP

0.60

MPC

0.52

ClinPred

0.42

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

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