chr7-155680607-T-G

Position:

• chr7-155680607-T-G

Variant summary

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

The NM_053043.3(RBM33):​c.266T>G​(p.Ile89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,446,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.24

Genes affected

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

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=0.3963481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3	c.266T>G	p.Ile89Ser	missense_variant	5/18	ENST00000401878.8	NP_444271.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8	c.266T>G	p.Ile89Ser	missense_variant	5/18	5	NM_053043.3	ENSP00000384160.3
RBM33	ENST00000392759.7	c.266T>G	p.Ile89Ser	missense_variant	5/7	5		ENSP00000376513.3
RBM33	ENST00000287912.7	c.266T>G	p.Ile89Ser	missense_variant	5/6	2		ENSP00000287912.3
RBM33	ENST00000307403.6	n.131T>G		non_coding_transcript_exon_variant	3/12	2		ENSP00000303878.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000622 AC: 9 AN: 1446836 Hom.: 0 Cov.: 32 AF XY: 0.00000974 AC XY: 7 AN XY: 718736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000814

Gnomad4 OTH exome AF: 0.00

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

Sep 27, 2024

The c.266T>G (p.I89S) alteration is located in exon 5 (coding exon 5) of the RBM33 gene. This alteration results from a T to G substitution at nucleotide position 266, causing the isoleucine (I) at amino acid position 89 to be replaced by a serine (S). 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	0.58
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	.;T;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-4.5	D;N;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.070	T;D;T
Polyphen		0.95	P;P;.
Vest4		0.82
MutPred		0.065		Gain of phosphorylation at I89 (P = 0.0555);Gain of phosphorylation at I89 (P = 0.0555);Gain of phosphorylation at I89 (P = 0.0555);
MVP		0.18
MPC		1.9
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.38
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr7-155473301;