3-49967920-C-G

Position:

• chr3-49967920-C-G

Variant summary

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

The NM_005777.3(RBM6):​c.495C>G​(p.Phe165Leu) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM6 NM_005777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0140

Genes affected

RBM6 (HGNC:9903): (RNA binding motif protein 6) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be active in nucleus. [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=0.2116858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM6	NM_005777.3	c.495C>G	p.Phe165Leu	missense_variant	3/21	ENST00000266022.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM6	ENST00000266022.9	c.495C>G	p.Phe165Leu	missense_variant	3/21	1	NM_005777.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

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 09, 2021

The c.495C>G (p.F165L) alteration is located in exon 3 (coding exon 2) of the RBM6 gene. This alteration results from a C to G substitution at nucleotide position 495, causing the phenylalanine (F) at amino acid position 165 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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.86	D;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.014	.;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.82	P;.
Vest4		0.42
MutPred		0.38		Loss of catalytic residue at F165 (P = 0.0057);.;
MVP		0.25
MPC		0.39
ClinPred		0.27	T
GERP RS		0.72
Varity_R		0.19
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-50005353;