chr7-155680859-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053043.3(RBM33):​c.518C>T​(p.Thr173Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000998 in 1,613,694 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: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: RBM33 NM_053043.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.060547203).

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>T	p.Thr173Ile	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>T	p.Thr173Ile	missense	Exon 5 of 18	ENSP00000384160.3	Q96EV2-1
	RBM33	ENST00000440108.5	TSL:5	c.191C>T	p.Thr64Ile	missense	Exon 1 of 6	ENSP00000394987.1	H7C0H2
	RBM33	ENST00000392759.7	TSL:5	c.518C>T	p.Thr173Ile	missense	Exon 5 of 7	ENSP00000376513.3	A8MTF7

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152174 Hom.: 0 Cov.: 32

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: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000563 AC: 14 AN: 248630 AF XY: 0.0000667

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000101 AC: 148 AN: 1461520 Hom.: 0 Cov.: 32 AF XY: 0.000109 AC XY: 79 AN XY: 727026

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000129 AC: 143 AN: 1111784

Other (OTH) AF: 0.0000497 AC: 3 AN: 60364

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000767 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000745 AC: 9

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

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	0.36
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.0
DANN	Uncertain	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.27
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.070
Sift	Benign	0.063	T
Sift4G	Benign	0.12	T
Polyphen		0.61	P
Vest4		0.15
MVP		0.10
MPC		1.4
ClinPred		0.12	T
GERP RS		-7.2
PromoterAI		-0.015	Neutral
Varity_R		0.054
gMVP		0.032
Mutation Taster		=91/9	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; COSMIC: COSV55297636;