3-49968204-G-C

Position:

• chr3-49968204-G-C

Variant summary

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

The NM_005777.3(RBM6):​c.779G>C​(p.Arg260Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBM6 NM_005777.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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]

RBM6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM6	NM_005777.3	c.779G>C	p.Arg260Thr	missense_variant	3/21	ENST00000266022.9	NP_005768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM6	ENST00000266022.9	c.779G>C	p.Arg260Thr	missense_variant	3/21	1	NM_005777.3	ENSP00000266022.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

May 10, 2022

The c.779G>C (p.R260T) alteration is located in exon 3 (coding exon 2) of the RBM6 gene. This alteration results from a G to C substitution at nucleotide position 779, causing the arginine (R) at amino acid position 260 to be replaced by a threonine (T). 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	0.72
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.060	T;T
Polyphen		1.0	D;.
Vest4		0.76
MutPred		0.35		Gain of glycosylation at T265 (P = 4e-04);.;
MVP		0.38
MPC		0.91
ClinPred		0.79	D
GERP RS		6.0
Varity_R		0.26
gMVP		0.17

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: rs1269876401; hg19: chr3-50005637;