7-155707032-C-G

Variant names:

• chr7-155707032-C-G
• NM_053043.3:c.912C>G

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.912C>G​(p.His304Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,415,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000028 (0 hom.)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.441
• 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=0.13671866).

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.912C>G	p.His304Gln	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.912C>G	p.His304Gln	missense	Exon 7 of 18	ENSP00000384160.3	Q96EV2-1
	RBM33	ENST00000392761.3	TSL:2	c.225C>G	p.His75Gln	missense	Exon 2 of 11	ENSP00000376514.3	H0Y3K4
	RBM33	ENST00000440108.5	TSL:5	c.585C>G	p.His195Gln	missense	Exon 3 of 6	ENSP00000394987.1	H7C0H2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1415186 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 699436

African (AFR) AF: 0.00 AC: 0 AN: 32272

American (AMR) AF: 0.000108 AC: 4 AN: 37092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25002

East Asian (EAS) AF: 0.00 AC: 0 AN: 37450

South Asian (SAS) AF: 0.00 AC: 0 AN: 80276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088182

Other (OTH) AF: 0.00 AC: 0 AN: 58652

GnomAD4 genome Cov.: 32

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	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.44
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.087
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.76	T
Polyphen		0.42	B
Vest4		0.28
MutPred		0.095		Gain of MoRF binding (P = 0.0854)
MVP		0.27
MPC		0.72
ClinPred		0.37	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.19
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr7-155499726;