chr7-155644910-G-C

Position:

• chr7-155644910-G-C

Variant summary

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

The NM_053043.3(RBM33):​c.34G>C​(p.Gly12Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.02

Genes affected

RBM33 (HGNC:27223): (RNA binding motif protein 33) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

RBM33-DT (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=0.28297335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3	c.34G>C	p.Gly12Arg	missense_variant	1/18	ENST00000401878.8	NP_444271.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8	c.34G>C	p.Gly12Arg	missense_variant	1/18	5	NM_053043.3	ENSP00000384160.3
RBM33	ENST00000392759.7	c.34G>C	p.Gly12Arg	missense_variant	1/7	5		ENSP00000376513.3
RBM33	ENST00000287912.7	c.34G>C	p.Gly12Arg	missense_variant	1/6	2		ENSP00000287912.3
RBM33-DT	ENST00000472015.2	n.75+221C>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Jul 07, 2024

The c.34G>C (p.G12R) alteration is located in exon 1 (coding exon 1) of the RBM33 gene. This alteration results from a G to C substitution at nucleotide position 34, causing the glycine (G) at amino acid position 12 to be replaced by an arginine (R). 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	0.65
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	.;T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;L;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.17	T;D;T
Sift4G	Benign	0.51	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.49
MutPred		0.089		Gain of methylation at G12 (P = 0.0287);Gain of methylation at G12 (P = 0.0287);Gain of methylation at G12 (P = 0.0287);
MVP		0.62
MPC		0.78
ClinPred		0.85	D
GERP RS		4.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.23
gMVP		0.034

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: rs1798131516; hg19: chr7-155437604;