7-92528851-A-G

Variant names:

• chr7-92528851-A-G
• rs764115541
• NM_032120.4:c.38A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/21 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
• 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]

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

PEX1 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 1A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics, Myriad Women’s Health
• Heimler syndrome 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• peroxisome biogenesis disorder 1B

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032120.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM48	NM_032120.4	MANE Select	c.38A>G	p.Asp13Gly	missense	Exon 1 of 5	NP_115496.2	Q5RL73-1
	RBM48	NM_001363366.1		c.38A>G	p.Asp13Gly	missense	Exon 1 of 6	NP_001350295.1
	RBM48	NM_001363367.1		c.-652A>G		5_prime_UTR	Exon 1 of 5	NP_001350296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM48	ENST00000265732.10	TSL:1 MANE Select	c.38A>G	p.Asp13Gly	missense	Exon 1 of 5	ENSP00000265732.5	Q5RL73-1
	RBM48	ENST00000481551.5	TSL:1	c.38A>G	p.Asp13Gly	missense	Exon 1 of 4	ENSP00000419242.1	Q5RL73-2
	RBM48	ENST00000496410.1	TSL:3	c.-396A>G		5_prime_UTR	Exon 1 of 3	ENSP00000418333.1	C9J787

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.14
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.010
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.16	B
Vest4		0.15
MutPred		0.36		Loss of stability (P = 0.0367)
MVP		0.42
MPC		0.28
ClinPred		0.070	T
GERP RS		0.48
PromoterAI		0.029	Neutral
Varity_R		0.066
gMVP		0.55
Mutation Taster		=97/3	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: rs764115541; hg19: chr7-92158165;