7-92532471-G-C

Position:

• chr7-92532471-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032120.4(RBM48):​c.370G>C​(p.Glu124Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM48 NM_032120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29

Genes affected

RBM48 (HGNC:21785): (RNA binding motif protein 48) Predicted to enable RNA binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM48	NM_032120.4	c.370G>C	p.Glu124Gln	missense_variant	3/5	ENST00000265732.10	NP_115496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM48	ENST00000265732.10	c.370G>C	p.Glu124Gln	missense_variant	3/5	1	NM_032120.4	ENSP00000265732.5
RBM48	ENST00000481551.5	c.370G>C	p.Glu124Gln	missense_variant	3/4	1		ENSP00000419242.1
RBM48	ENST00000496410.1	c.196G>C	p.Glu66Gln	missense_variant	3/3	3		ENSP00000418333.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 18, 2023

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 124 of the RBM48 protein (p.Glu124Gln). This variant has not been reported in the literature in individuals affected with RBM48-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RBM48 protein function. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	2.0	M;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0040	D;D;T
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.67
MutPred		0.59		Loss of disorder (P = 0.1829);Loss of disorder (P = 0.1829);.;
MVP		0.81
MPC		0.80
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92161785;