Genetic Variant NM_053043.3:c.14T>G (chr7-155644890-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_053043.3(RBM33):c.14T>G(p.Leu5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,498,470 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: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

RBM33
NM_053043.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

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

RBM33 links:

RBM33-DT (HGNC:56024): (RBM33 divergent transcript)

RBM33-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3032086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM33	NM_053043.3 link	c.14T>G	p.Leu5Arg	missense_variant	Exon 1 of 18	ENST00000401878.8	NP_444271.2	Q96EV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM33	ENST00000401878.8 link	c.14T>G	p.Leu5Arg	missense_variant	Exon 1 of 18	5	NM_053043.3	ENSP00000384160.3	Q96EV2-1
RBM33	ENST00000392759.7 link	c.14T>G	p.Leu5Arg	missense_variant	Exon 1 of 7	5		ENSP00000376513.3	A8MTF7
RBM33	ENST00000287912.7 link	c.14T>G	p.Leu5Arg	missense_variant	Exon 1 of 6	2		ENSP00000287912.3	Q96EV2-2
RBM33-DT	ENST00000472015.2 link	n.75+241A>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

97302

Hom.:

AF XY:

0.000128

AC XY:

AN XY:

54542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000100

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000564

AC:

AN:

1346376

Hom.:

Cov.:

AF XY:

0.0000693

AC XY:

AN XY:

663472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000945

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000264

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000650

Gnomad4 OTH exome

AF:

0.0000178

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14T>G (p.L5R) alteration is located in exon 1 (coding exon 1) of the RBM33 gene. This alteration results from a T to G substitution at nucleotide position 14, causing the leucine (L) at amino acid position 5 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

.;T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.40

T;T;T

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.22

Sift

Pathogenic

0.0

D;D;D

Sift4G

Benign

0.097

T;D;T

Polyphen

0.99

D;D;.

Vest4

0.43

MutPred

0.17

Gain of methylation at L5 (P = 0.0018);Gain of methylation at L5 (P = 0.0018);Gain of methylation at L5 (P = 0.0018);

MVP

0.35

MPC

0.96

ClinPred

0.20

GERP RS

3.9

Varity_R

0.48

gMVP

0.091

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over