18-80045851-C-G

Position:

• chr18-80045851-C-G

Variant summary

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

The NM_024805.3(RBFA):​c.728C>G​(p.Ala243Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBFA NM_024805.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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]

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=0.22703195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFA	NM_024805.3	c.728C>G	p.Ala243Gly	missense_variant	7/7	ENST00000306735.10	NP_079081.2
RBFA	NM_001171967.2	c.643C>G	p.Arg215Gly	missense_variant	6/6		NP_001165438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFA	ENST00000306735.10	c.728C>G	p.Ala243Gly	missense_variant	7/7	1	NM_024805.3	ENSP00000305696	P1
RBFA	ENST00000262197.7	c.643C>G	p.Arg215Gly	missense_variant	6/6	1		ENSP00000262197
RBFA	ENST00000593019.1	n.1070C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000446 AC: 1 AN: 224196 Hom.: 0 AF XY: 0.00000835 AC XY: 1 AN XY: 119702

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: 0.00000974

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

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

Aug 23, 2021

The c.728C>G (p.A243G) alteration is located in exon 7 (coding exon 7) of the RBFA gene. This alteration results from a C to G substitution at nucleotide position 728, causing the alanine (A) at amino acid position 243 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.64	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.093
Sift	Benign	0.076	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.29		Loss of helix (P = 0.0304);
MVP		0.27
MPC		0.77
ClinPred		0.88	D
GERP RS		3.9
Varity_R		0.093
gMVP		0.14

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

Other links and lift over

dbSNP: rs374705895; hg19: chr18-77805851;