rs770898461

Variant names:

• chr2-178112575-G-A
• rs770898461
• NM_152945.4:c.29G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-178112575-G-A
• chr2-178112575-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152945.4(RBM45):​c.29G>A​(p.Gly10Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. G10V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RBM45 NM_152945.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

Genes affected

RBM45 (HGNC:24468): (RNA binding motif protein 45) This gene encodes a member of the RNA recognition motif (RRM)-type RNA-binding family of proteins. This protein exhibits preferential binding to poly(C) RNA. Initial cloning of this gene found that the rat ortholog was dynamically expressed in the developing rat brain. This protein has been localized to inclusion bodies in the brain and spinal cord of amyotrophic lateral sclerosis and Alzheimer's patients. A pseudogene has been identified on chromosome 8. [provided by RefSeq, Feb 2015]

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=0.13849947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM45	NM_152945.4	c.29G>A	p.Gly10Asp	missense_variant	Exon 1 of 10	ENST00000286070.10	NP_694453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM45	ENST00000286070.10	c.29G>A	p.Gly10Asp	missense_variant	Exon 1 of 10	1	NM_152945.4	ENSP00000286070.5
RBM45	ENST00000424000.6	n.152G>A		non_coding_transcript_exon_variant	Exon 1 of 9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426570 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 705148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33334

American (AMR) AF: 0.00 AC: 0 AN: 43374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 76816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50248

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095438

Other (OTH) AF: 0.00 AC: 0 AN: 59238

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PhyloP100		3.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	0.16	.;N
REVEL	Benign	0.037
Sift	Uncertain	0.021	.;D
Sift4G	Benign	0.29	T;T
Polyphen		0.0020	.;B
Vest4		0.30
MutPred		0.23		Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);
MVP		0.30
MPC		0.75
ClinPred		0.52	D
GERP RS		4.5
PromoterAI		-0.024	Neutral
Varity_R		0.19
gMVP		0.31
Mutation Taster		=90/10	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: rs770898461; hg19: chr2-178977302;