Variant 18-80045980-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024805.3(RBFA):c.857T>C(p.Leu286Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,461,852 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: 0.000046 ( 0 hom. )

Consequence

RBFA
NM_024805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.64

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06295577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFA	NM_024805.3 linkuse as main transcript	c.857T>C	p.Leu286Pro	missense_variant	7/7	ENST00000306735.10	NP_079081.2
RBFA	NM_001171967.2 linkuse as main transcript	c.*43T>C		3_prime_UTR_variant	6/6		NP_001165438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFA	ENST00000306735.10 linkuse as main transcript	c.857T>C	p.Leu286Pro	missense_variant	7/7	1	NM_024805.3	ENSP00000305696	P1	Q8N0V3-1
RBFA	ENST00000262197.7 linkuse as main transcript	c.*43T>C		3_prime_UTR_variant	6/6	1		ENSP00000262197		Q8N0V3-2
RBFA	ENST00000593019.1 linkuse as main transcript	n.1199T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251322

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000531

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000903

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jun 07, 2023

The c.857T>C (p.L286P) alteration is located in exon 7 (coding exon 7) of the RBFA gene. This alteration results from a T to C substitution at nucleotide position 857, causing the leucine (L) at amino acid position 286 to be replaced by a proline (P). 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

0.058

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.018

DANN

Benign

0.33

DEOGEN2

Benign

0.00026

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.23

M_CAP

Benign

0.0035

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.090

REVEL

Benign

0.040

Sift

Benign

0.23

Sift4G

Benign

0.22

Polyphen

0.28

Vest4

0.10

MVP

0.076

MPC

0.32

ClinPred

0.080

GERP RS

-8.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.061

gMVP

0.047

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

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