18-80038613-A-C

Position:

• chr18-80038613-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000306735.10(RBFA):​c.487A>C​(p.Met163Leu) 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. 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)
• Consequence: RBFA ENST00000306735.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

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]

ENSG00000267127 (HGNC:):

ACMG classification

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=0.28455085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFA	NM_024805.3	c.487A>C	p.Met163Leu	missense_variant	4/7	ENST00000306735.10	NP_079081.2
RBFA	NM_001171967.2	c.487A>C	p.Met163Leu	missense_variant	4/6		NP_001165438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFA	ENST00000306735.10	c.487A>C	p.Met163Leu	missense_variant	4/7	1	NM_024805.3	ENSP00000305696.4
ENSG00000267127	ENST00000569722.5	n.158+3960A>C		intron_variant		2		ENSP00000468252.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Nov 22, 2021

The c.487A>C (p.M163L) alteration is located in exon 4 (coding exon 4) of the RBFA gene. This alteration results from a A to C substitution at nucleotide position 487, causing the methionine (M) at amino acid position 163 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.0012	T;.
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.84	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.056
Sift	Benign	0.27	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.10	B;B
Vest4		0.54
MutPred		0.39		Loss of MoRF binding (P = 0.0803);Loss of MoRF binding (P = 0.0803);
MVP		0.32
MPC		0.23
ClinPred		0.24	T
GERP RS		2.1
Varity_R		0.050
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-77798613;