15-64748517-G-T

Variant names:

• chr15-64748517-G-T
• rs200454835
• NM_194272.3:c.469C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_194272.3(RBPMS2):​c.469C>A​(p.Pro157Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBPMS2 NM_194272.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66
• Publications: 0 publications found

Genes affected

RBPMS2 (HGNC:19098): (RNA binding protein, mRNA processing factor 2) The protein encoded by this gene is a member of the RNA recognition motif (RRM)-containing protein family and is involved in the development and dedifferentiation of digestive smooth muscle cells. The encoded protein functions as a homodimer and indirectly inhibits the bone morphogenetic protein pathway. [provided by RefSeq, Aug 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194272.3. 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
	RBPMS2	NM_194272.3	MANE Select	c.469C>A	p.Pro157Thr	missense	Exon 6 of 8	NP_919248.1	Q6ZRY4-1
	RBPMS2	NR_138350.2		n.700C>A		non_coding_transcript_exon	Exon 6 of 8
	RBPMS2	NR_138363.2		n.470C>A		non_coding_transcript_exon	Exon 6 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBPMS2	ENST00000300069.5	TSL:1 MANE Select	c.469C>A	p.Pro157Thr	missense	Exon 6 of 8	ENSP00000300069.4	Q6ZRY4-1
	RBPMS2	ENST00000890183.1		c.469C>A	p.Pro157Thr	missense	Exon 6 of 7	ENSP00000560242.1
	RBPMS2	ENST00000890184.1		c.469C>A	p.Pro157Thr	missense	Exon 6 of 8	ENSP00000560243.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.48	P
Vest4		0.89
MutPred		0.45		Gain of helix (P = 0.0696)
MVP		0.37
MPC		1.1
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.47
gMVP		0.71

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: rs200454835; hg19: chr15-65040716;