7-155706973-T-G

Variant names:

• chr7-155706973-T-G
• rs368447642
• NM_053043.3:c.853T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_053043.3(RBM33):​c.853T>G​(p.Cys285Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,598,018 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C285Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (1 hom.)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.095478415).

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.853T>G	p.Cys285Gly	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.853T>G	p.Cys285Gly	missense	Exon 7 of 18	ENSP00000384160.3	Q96EV2-1
	RBM33	ENST00000392761.3	TSL:2	c.166T>G	p.Cys56Gly	missense	Exon 2 of 11	ENSP00000376514.3	H0Y3K4
	RBM33	ENST00000440108.5	TSL:5	c.526T>G	p.Cys176Gly	missense	Exon 3 of 6	ENSP00000394987.1	H7C0H2

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000453 AC: 10 AN: 220940 AF XY: 0.0000422

Gnomad AFR exome AF: 0.000625

Gnomad AMR exome AF: 0.0000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000491 AC: 71 AN: 1445956 Hom.: 1 Cov.: 31 AF XY: 0.0000376 AC XY: 27 AN XY: 717228

African (AFR) AF: 0.00123 AC: 41 AN: 33232

American (AMR) AF: 0.0000474 AC: 2 AN: 42152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 39236

South Asian (SAS) AF: 0.0000482 AC: 4 AN: 82950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52546

Middle Eastern (MID) AF: 0.000348 AC: 2 AN: 5752

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1104400

Other (OTH) AF: 0.000300 AC: 18 AN: 59958

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74298

African (AFR) AF: 0.000580 AC: 24 AN: 41398

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000372 Hom.: 0

Bravo AF: 0.000178

ESP6500AA AF: 0.000709 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000496 AC: 6

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	0.13
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.39	T
Polyphen		0.0020	B
Vest4		0.52
MVP		0.16
MPC		1.9
ClinPred		0.086	T
GERP RS		3.4
Varity_R		0.38
gMVP		0.23
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs368447642; hg19: chr7-155499667;