7-92528851-A-G

Position:

• chr7-92528851-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032120.4(RBM48):​c.38A>G​(p.Asp13Gly) 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 benign outcome for this variant. 14/20 in silico tools predict a benign 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: 0.135

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14983088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM48	NM_032120.4	c.38A>G	p.Asp13Gly	missense_variant	1/5	ENST00000265732.10	NP_115496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM48	ENST00000265732.10	c.38A>G	p.Asp13Gly	missense_variant	1/5	1	NM_032120.4	ENSP00000265732.5
RBM48	ENST00000481551.5	c.38A>G	p.Asp13Gly	missense_variant	1/4	1		ENSP00000419242.1
RBM48	ENST00000496410	c.-396A>G		5_prime_UTR_variant	1/3	3		ENSP00000418333.1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2021

The c.38A>G (p.D13G) alteration is located in exon 1 (coding exon 1) of the RBM48 gene. This alteration results from a A to G substitution at nucleotide position 38, causing the aspartic acid (D) at amino acid position 13 to be replaced by a glycine (G). 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	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.046	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.010
Sift	Benign	0.12	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.16	B;.
Vest4		0.15
MutPred		0.36		Loss of stability (P = 0.0367);Loss of stability (P = 0.0367);
MVP		0.42
MPC		0.28
ClinPred		0.070	T
GERP RS		0.48
Varity_R		0.066
gMVP		0.55

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: chr7-92158165;