chr7-155680604-C-A

Position:

• chr7-155680604-C-A

Variant summary

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

The NM_053043.3(RBM33):​c.263C>A​(p.Thr88Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,444,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17566448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3	c.263C>A	p.Thr88Lys	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.263C>A	p.Thr88Lys	missense_variant	5/18	5	NM_053043.3	ENSP00000384160.3
RBM33	ENST00000392759.7	c.263C>A	p.Thr88Lys	missense_variant	5/7	5		ENSP00000376513.3
RBM33	ENST00000287912.7	c.263C>A	p.Thr88Lys	missense_variant	5/6	2		ENSP00000287912.3
RBM33	ENST00000307403.6	n.128C>A		non_coding_transcript_exon_variant	3/12	2		ENSP00000303878.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444962 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717652

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Oct 26, 2022

The c.263C>A (p.T88K) alteration is located in exon 5 (coding exon 5) of the RBM33 gene. This alteration results from a C to A substitution at nucleotide position 263, causing the threonine (T) at amino acid position 88 to be replaced by a lysine (K). 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	0.27
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.054	.;T;.
Eigen	Benign	0.075
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.6	D;N;D
REVEL	Benign	0.045
Sift	Benign	0.072	T;D;T
Sift4G	Benign	0.28	T;D;T
Polyphen		0.99	D;B;.
Vest4		0.37
MutPred		0.15		Gain of ubiquitination at T88 (P = 0.0039);Gain of ubiquitination at T88 (P = 0.0039);Gain of ubiquitination at T88 (P = 0.0039);
MVP		0.19
MPC		1.0
ClinPred		0.41	T
GERP RS		4.8
Varity_R		0.22
gMVP		0.12

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: rs1799311660; hg19: chr7-155473298;