8-30385129-C-A

Variant names:

• chr8-30385129-C-A
• rs1396646389
• NM_001008710.3:c.37C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008710.3(RBPMS):​c.37C>A​(p.Pro13Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBPMS NM_001008710.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

Genes affected

RBPMS (HGNC:19097): (RNA binding protein, mRNA processing factor) This gene encodes a member of the RNA recognition motif family of RNA-binding proteins. The RNA recognition motif is between 80-100 amino acids in length and family members contain one to four copies of the motif. The RNA recognition motif consists of two short stretches of conserved sequence, as well as a few highly conserved hydrophobic residues. The encoded protein has a single, putative RNA recognition motif in its N-terminus. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

RBPMS-AS1 (HGNC:48721): (RBPMS antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09749144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBPMS	NM_001008710.3	c.37C>A	p.Pro13Thr	missense_variant	Exon 1 of 9	ENST00000397323.9	NP_001008710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBPMS	ENST00000397323.9	c.37C>A	p.Pro13Thr	missense_variant	Exon 1 of 9	1	NM_001008710.3	ENSP00000380486.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1375254 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.068	T;.;T;.;T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.76	.;T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.097	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L;L;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.050	N;N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.11	T;D;T;D;D
Sift4G	Benign	0.096	T;T;T;T;T
Polyphen		0.20	B;B;B;B;B
Vest4		0.12
MutPred		0.26		Loss of phosphorylation at T12 (P = 0.0553);Loss of phosphorylation at T12 (P = 0.0553);Loss of phosphorylation at T12 (P = 0.0553);Loss of phosphorylation at T12 (P = 0.0553);Loss of phosphorylation at T12 (P = 0.0553);
MVP		0.26
MPC		0.99
ClinPred		0.14	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.045
gMVP		0.45

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

LitVar

Other links and lift over

dbSNP: rs1396646389; hg19: chr8-30242645;