7-92528817-G-C

Variant names:

• chr7-92528817-G-C
• rs1793446137
• NM_032120.4:c.4G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032120.4(RBM48):​c.4G>C​(p.Ala2Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: RBM48 NM_032120.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.08

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM48	NM_032120.4	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 5	ENST00000265732.10	NP_115496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM48	ENST00000265732.10	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 5	1	NM_032120.4	ENSP00000265732.5
RBM48	ENST00000481551.5	c.4G>C	p.Ala2Pro	missense_variant	Exon 1 of 4	1		ENSP00000419242.1
RBM48	ENST00000496410	c.-430G>C		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000418333.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4G>C (p.A2P) alteration is located in exon 1 (coding exon 1) of the RBM48 gene. This alteration results from a G to C substitution at nucleotide position 4, causing the alanine (A) at amino acid position 2 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.26		Gain of glycosylation at A2 (P = 0.0407);Gain of glycosylation at A2 (P = 0.0407);
MVP		0.81
MPC		0.92
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.52
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs1793446137; hg19: chr7-92158131;