NM_053043.3:c.941C>T

Variant names:

• chr7-155707061-C-T
• rs960338144
• NM_053043.3:c.941C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053043.3(RBM33):​c.941C>T​(p.Pro314Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,391,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 3.48
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10906139).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053043.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM33	NM_053043.3	MANE Select	c.941C>T	p.Pro314Leu	missense	Exon 7 of 18	NP_444271.2	Q96EV2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM33	ENST00000401878.8	TSL:5 MANE Select	c.941C>T	p.Pro314Leu	missense	Exon 7 of 18	ENSP00000384160.3	Q96EV2-1
	RBM33	ENST00000392761.3	TSL:2	c.254C>T	p.Pro85Leu	missense	Exon 2 of 11	ENSP00000376514.3	H0Y3K4
	RBM33	ENST00000440108.5	TSL:5	c.614C>T	p.Pro205Leu	missense	Exon 3 of 6	ENSP00000394987.1	H7C0H2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000659 AC: 1 AN: 151736 AF XY: 0.0000124

Gnomad AFR exome AF: 0.000119

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1391164 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 2 AN XY: 686172

African (AFR) AF: 0.0000648 AC: 2 AN: 30866

American (AMR) AF: 0.00 AC: 0 AN: 32934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24090

East Asian (EAS) AF: 0.00 AC: 0 AN: 36186

South Asian (SAS) AF: 0.00 AC: 0 AN: 78758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075974

Other (OTH) AF: 0.00 AC: 0 AN: 57472

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.036
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.28	B
Vest4		0.35
MutPred		0.22		Loss of catalytic residue at P313 (P = 0.0165)
MVP		0.068
MPC		1.5
ClinPred		0.28	T
GERP RS		5.0
Varity_R		0.061
gMVP		0.16
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs960338144; hg19: chr7-155499755;