Variant 18-80038554-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000306735.10(RBFA):c.428C>A(p.Thr143Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000089 ( 0 hom. )

Consequence

RBFA
ENST00000306735.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.208

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:

ENSG00000267127 (HGNC:):

ENSG00000267127 links:

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ACMG classification

Classification made for transcript

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=0.08240324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFA	NM_024805.3 linkuse as main transcript	c.428C>A	p.Thr143Lys	missense_variant	4/7	ENST00000306735.10	NP_079081.2	Q8N0V3-1
RBFA	NM_001171967.2 linkuse as main transcript	c.428C>A	p.Thr143Lys	missense_variant	4/6		NP_001165438.1	Q8N0V3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFA	ENST00000306735.10 linkuse as main transcript	c.428C>A	p.Thr143Lys	missense_variant	4/7	1	NM_024805.3	ENSP00000305696.4		Q8N0V3-1
ENSG00000267127	ENST00000569722.5 linkuse as main transcript	n.158+3901C>A		intron_variant		2		ENSP00000468252.1		K7EIM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251326

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

Nov 21, 2022

The c.428C>A (p.T143K) alteration is located in exon 4 (coding exon 4) of the RBFA gene. This alteration results from a C to A substitution at nucleotide position 428, causing the threonine (T) at amino acid position 143 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0047

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.023

Sift

Benign

0.15

T;T

Sift4G

Uncertain

0.037

D;D

Polyphen

0.13

B;P

Vest4

0.40

MutPred

0.39

Gain of ubiquitination at T143 (P = 0.0146);Gain of ubiquitination at T143 (P = 0.0146);

MVP

0.41

MPC

0.30

ClinPred

0.22

GERP RS

1.9

Varity_R

0.072

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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