7-155737585-A-C

Position:

• chr7-155737585-A-C

Variant summary

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

The NM_053043.3(RBM33):​c.1316A>C​(p.Gln439Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.51

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=0.21310067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM33	NM_053043.3	c.1316A>C	p.Gln439Pro	missense_variant	10/18	ENST00000401878.8	NP_444271.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM33	ENST00000401878.8	c.1316A>C	p.Gln439Pro	missense_variant	10/18	5	NM_053043.3	ENSP00000384160	P3
RBM33	ENST00000392761.3	c.632A>C	p.Gln211Pro	missense_variant	5/11	2		ENSP00000376514
RBM33	ENST00000440108.5	c.1019A>C	p.Gln340Pro	missense_variant	6/6	5		ENSP00000394987
RBM33	ENST00000307403.6	c.*413A>C		3_prime_UTR_variant, NMD_transcript_variant	9/12	2		ENSP00000303878

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Nov 01, 2021

The c.1316A>C (p.Q439P) alteration is located in exon 10 (coding exon 10) of the RBM33 gene. This alteration results from a A to C substitution at nucleotide position 1316, causing the glutamine (Q) at amino acid position 439 to be replaced by a proline (P). 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	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.61	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.56	T;T
Polyphen		0.11	B;.
Vest4		0.64
MutPred		0.17		Gain of glycosylation at Q439 (P = 0.0174);.;
MVP		0.56
MPC		0.37
ClinPred		0.56	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-155530279;