rs754057902

Variant names:

• chr8-93734247-G-A
• rs754057902
• NM_001377960.1:c.2164C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-93734247-G-A
• chr8-93734247-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377960.1(RBM12B):​c.2164C>T​(p.His722Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,610,080 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: RBM12B NM_001377960.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.08
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06114313).

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.2164C>T	p.His722Tyr	missense	Exon 4 of 4	NP_001364889.1	Q8IXT5
	RBM12B	NM_001377961.1		c.2164C>T	p.His722Tyr	missense	Exon 5 of 5	NP_001364890.1	Q8IXT5
	RBM12B	NM_001377962.1		c.2164C>T	p.His722Tyr	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.2164C>T	p.His722Tyr	missense	Exon 4 of 4	ENSP00000429807.2	Q8IXT5
	RBM12B	ENST00000517700.6	TSL:1	c.2164C>T	p.His722Tyr	missense	Exon 3 of 3	ENSP00000427729.2	Q8IXT5
	RBM12B	ENST00000399300.7	TSL:2	c.2164C>T	p.His722Tyr	missense	Exon 3 of 3	ENSP00000382239.2	Q8IXT5

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151194 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000122 AC: 3 AN: 245338 AF XY: 0.00000750

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1458886 Hom.: 0 Cov.: 34 AF XY: 0.0000124 AC XY: 9 AN XY: 725600

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 85990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1110582

Other (OTH) AF: 0.00 AC: 0 AN: 60192

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151194 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73774

African (AFR) AF: 0.00 AC: 0 AN: 41136

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67716

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions as Germline

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	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.036
Sift	Uncertain	0.013	D
Sift4G	Benign	0.13	T
Polyphen		0.20	B
Vest4		0.14
MutPred		0.25		Gain of phosphorylation at H722 (P = 0.0137)
MVP		0.44
ClinPred		0.10	T
GERP RS		2.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.072
gMVP		0.12
Mutation Taster		=98/2	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: rs754057902; hg19: chr8-94746475;