chr7-155707061-C-T

Position:

• chr7-155707061-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

RBM33 (HGNC:):

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=0.10906139).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3	c.941C>T	p.Pro314Leu	missense_variant	7/18	ENST00000401878.8	NP_444271.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8	c.941C>T	p.Pro314Leu	missense_variant	7/18	5	NM_053043.3	ENSP00000384160.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000659 AC: 1 AN: 151736 Hom.: 0 AF XY: 0.0000124 AC XY: 1 AN XY: 80356

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 SAS 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

Gnomad4 AFR exome AF: 0.0000648

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Feb 06, 2023

The c.941C>T (p.P314L) alteration is located in exon 7 (coding exon 7) of the RBM33 gene. This alteration results from a C to T substitution at nucleotide position 941, causing the proline (P) at amino acid position 314 to be replaced by a leucine (L). 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	0.099
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;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.036
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.0060	D;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs960338144; hg19: chr7-155499755;