7-92528838-G-T

Variant names:

• chr7-92528838-G-T
• rs367557608
• NM_032120.4:c.25G>T

Variant summary

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

The NM_032120.4(RBM48):​c.25G>T​(p.Gly9Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G9R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RBM48 NM_032120.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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.25G>T	p.Gly9Trp	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.25G>T	p.Gly9Trp	missense_variant	Exon 1 of 5	1	NM_032120.4	ENSP00000265732.5
RBM48	ENST00000481551.5	c.25G>T	p.Gly9Trp	missense_variant	Exon 1 of 4	1		ENSP00000419242.1
RBM48	ENST00000496410.1	c.-409G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	3		ENSP00000418333.1
RBM48	ENST00000496410.1	c.-409G>T		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000418333.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461784 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33472

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.5	M;M
PhyloP100		6.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;.
Vest4		0.58
MutPred		0.40		Gain of catalytic residue at G9 (P = 0.007);Gain of catalytic residue at G9 (P = 0.007);
MVP		0.82
MPC		0.88
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		0.072	Neutral
Varity_R		0.20
gMVP		0.56
Mutation Taster		=84/16	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

dbSNP: rs367557608; hg19: chr7-92158152; COSMIC: COSV99720361; COSMIC: COSV99720361;