chr8-93734036-T-C

Variant names:

• chr8-93734036-T-C
• rs932536801
• NM_001377960.1:c.2375A>G

Variant summary

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

The NM_001377960.1(RBM12B):​c.2375A>G​(p.Gln792Arg) 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. 15/22 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. Q792P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RBM12B NM_001377960.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 0 publications found

Genes affected

RBM12B (HGNC:32310): (RNA binding motif protein 12B) Enables RNA binding activity. Predicted to be involved in regulation of RNA splicing. Predicted to be part of ribonucleoprotein complex. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253722 (HGNC:):

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=0.08071989).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377960.1. 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
	RBM12B	NM_001377960.1	MANE Select	c.2375A>G	p.Gln792Arg	missense	Exon 4 of 4	NP_001364889.1	Q8IXT5
	RBM12B	NM_001377961.1		c.2375A>G	p.Gln792Arg	missense	Exon 5 of 5	NP_001364890.1	Q8IXT5
	RBM12B	NM_001377962.1		c.2375A>G	p.Gln792Arg	missense	Exon 3 of 3	NP_001364891.1	Q8IXT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM12B	ENST00000520560.6	TSL:2 MANE Select	c.2375A>G	p.Gln792Arg	missense	Exon 4 of 4	ENSP00000429807.2	Q8IXT5
	RBM12B	ENST00000517700.6	TSL:1	c.2375A>G	p.Gln792Arg	missense	Exon 3 of 3	ENSP00000427729.2	Q8IXT5
	RBM12B	ENST00000399300.7	TSL:2	c.2375A>G	p.Gln792Arg	missense	Exon 3 of 3	ENSP00000382239.2	Q8IXT5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.039
Sift	Uncertain	0.025	D
Sift4G	Benign	0.46	T
Polyphen		0.49	P
Vest4		0.26
MutPred		0.27		Gain of MoRF binding (P = 0.0141)
MVP		0.12
ClinPred		0.13	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.072
gMVP		0.077
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: rs932536801; hg19: chr8-94746264;