chr7-155678615-C-T

Variant names:

• chr7-155678615-C-T
• rs762099807
• NM_053043.3:c.179C>T

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.179C>T​(p.Ser60Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,555,454 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13
• 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=0.16121614).

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.179C>T	p.Ser60Leu	missense	Exon 4 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.179C>T	p.Ser60Leu	missense	Exon 4 of 18	ENSP00000384160.3	Q96EV2-1
	RBM33	ENST00000392759.7	TSL:5	c.179C>T	p.Ser60Leu	missense	Exon 4 of 7	ENSP00000376513.3	A8MTF7
	RBM33	ENST00000287912.7	TSL:2	c.179C>T	p.Ser60Leu	missense	Exon 4 of 6	ENSP00000287912.3	Q96EV2-2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 33

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000996 AC: 2 AN: 200810 AF XY: 0.00000928

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000345

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000207 AC: 29 AN: 1403438 Hom.: 0 Cov.: 25 AF XY: 0.0000215 AC XY: 15 AN XY: 696612

African (AFR) AF: 0.00 AC: 0 AN: 31820

American (AMR) AF: 0.00 AC: 0 AN: 39686

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 37872

South Asian (SAS) AF: 0.00 AC: 0 AN: 79346

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.0000233 AC: 25 AN: 1074760

Other (OTH) AF: 0.0000516 AC: 3 AN: 58184

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74240

African (AFR) AF: 0.00 AC: 0 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10572

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67996

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

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000833 AC: 1

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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.1
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Benign	0.35	T
Polyphen		0.11	B
Vest4		0.40
MutPred		0.14		Loss of phosphorylation at S60 (P = 0.0166)
MVP		0.68
MPC		0.91
ClinPred		0.66	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.16
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs762099807; hg19: chr7-155471309; COSMIC: COSV105137824; COSMIC: COSV105137824;