chr8-93733421-T-G

Position:

• chr8-93733421-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001377960.1(RBM12B):​c.2990A>C​(p.Lys997Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM12B NM_001377960.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35260272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM12B	NM_001377960.1	c.2990A>C	p.Lys997Thr	missense_variant	4/4	ENST00000520560.6	NP_001364889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM12B	ENST00000520560.6	c.2990A>C	p.Lys997Thr	missense_variant	4/4	2	NM_001377960.1	ENSP00000429807.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.2990A>C (p.K997T) alteration is located in exon 3 (coding exon 1) of the RBM12B gene. This alteration results from a A to C substitution at nucleotide position 2990, causing the lysine (K) at amino acid position 997 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.6	D;D;.
REVEL	Benign	0.13
Sift	Uncertain	0.023	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.43
MutPred		0.44		Loss of MoRF binding (P = 0.0071);.;.;
MVP		0.46
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.25
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-94745649;