7-92528858-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032120.4(RBM48):​c.45C>A​(p.His15Gln) variant causes a missense change involving the alteration of a non-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

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBM48NM_032120.4 linkc.45C>A p.His15Gln missense_variant 1/5 ENST00000265732.10 NP_115496.2 Q5RL73-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RBM48ENST00000265732.10 linkc.45C>A p.His15Gln missense_variant 1/51 NM_032120.4 ENSP00000265732.5 Q5RL73-1
RBM48ENST00000481551.5 linkc.45C>A p.His15Gln missense_variant 1/41 ENSP00000419242.1 Q5RL73-2
RBM48ENST00000496410.1 linkc.-389C>A 5_prime_UTR_variant 1/33 ENSP00000418333.1 C9J787

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 17, 2023The c.45C>A (p.H15Q) alteration is located in exon 1 (coding exon 1) of the RBM48 gene. This alteration results from a C to A substitution at nucleotide position 45, causing the histidine (H) at amino acid position 15 to be replaced by a glutamine (Q). 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
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.51
T;T
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.95
D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-6.4
D;D
REVEL
Pathogenic
0.78
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.021
D;D
Polyphen
1.0
D;.
Vest4
0.80
MutPred
0.77
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
0.77
MPC
0.81
ClinPred
1.0
D
GERP RS
2.9
Varity_R
0.84
gMVP
0.51

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: chr7-92158172; API