NM_053043.3:c.518C>G

Variant names:

• chr7-155680859-C-G
• rs765048302
• NM_053043.3:c.518C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053043.3(RBM33):​c.518C>G​(p.Thr173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T173I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02101165).

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.518C>G	p.Thr173Ser	missense	Exon 5 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.518C>G	p.Thr173Ser	missense	Exon 5 of 18	ENSP00000384160.3	Q96EV2-1
	RBM33	ENST00000440108.5	TSL:5	c.191C>G	p.Thr64Ser	missense	Exon 1 of 6	ENSP00000394987.1	H7C0H2
	RBM33	ENST00000392759.7	TSL:5	c.518C>G	p.Thr173Ser	missense	Exon 5 of 7	ENSP00000376513.3	A8MTF7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248630 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.27
DANN	Benign	0.68
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.27
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.040
Sift	Benign	0.82	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.085
MutPred		0.12		Gain of glycosylation at T173 (P = 0.1937)
MVP		0.19
MPC		0.61
ClinPred		0.025	T
GERP RS		-7.2
PromoterAI		-0.028	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.028
gMVP		0.014
Mutation Taster		=97/3	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

dbSNP: rs765048302; hg19: chr7-155473553;