NM_033117.4:c.375G>C

Variant names:

• chr9-122245294-C-G
• NM_033117.4:c.375G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033117.4(RBM18):​c.375G>C​(p.Glu125Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,822 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBM18 NM_033117.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.886
• Publications: 0 publications found

Genes affected

RBM18 (HGNC:28413): (RNA binding motif protein 18) Predicted to enable RNA binding activity. Located in cytosol; intercellular bridge; and nucleoplasm. [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=0.25417382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033117.4. 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
	RBM18	NM_033117.4	MANE Select	c.375G>C	p.Glu125Asp	missense	Exon 5 of 6	NP_149108.1	Q96H35
	RBM18	NR_027125.2		n.517G>C		non_coding_transcript_exon	Exon 5 of 7
	RBM18	NR_027126.2		n.611G>C		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM18	ENST00000417201.4	TSL:1 MANE Select	c.375G>C	p.Glu125Asp	missense	Exon 5 of 6	ENSP00000409315.2	Q96H35
	RBM18	ENST00000483428.1	TSL:1	n.565G>C		non_coding_transcript_exon	Exon 6 of 7
	RBM18	ENST00000870819.1		c.408G>C	p.Glu136Asp	missense	Exon 5 of 6	ENSP00000540878.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458822 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 725920

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109276

Other (OTH) AF: 0.00 AC: 0 AN: 60294

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.89
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.15
Sift	Benign	0.42	T
Sift4G	Benign	0.62	T
Polyphen		0.96	P
Vest4		0.48
MutPred		0.16		Loss of glycosylation at S127 (P = 0.1234)
MVP		0.18
MPC		0.68
ClinPred		0.60	D
GERP RS		2.9
Varity_R		0.096
gMVP		0.32
Mutation Taster		=53/47	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: chr9-125007573;