rs141658779

Variant names:

• chr15-64748424-C-T
• rs141658779
• NM_194272.3:c.562G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_194272.3(RBPMS2):​c.562G>A​(p.Ala188Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000111 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: RBPMS2 NM_194272.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.99
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10180348).

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.562G>A	p.Ala188Thr	missense	Exon 6 of 8	NP_919248.1	Q6ZRY4-1
	RBPMS2	NR_138350.2		n.793G>A		non_coding_transcript_exon	Exon 6 of 8
	RBPMS2	NR_138363.2		n.563G>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.562G>A	p.Ala188Thr	missense	Exon 6 of 8	ENSP00000300069.4	Q6ZRY4-1
	RBPMS2	ENST00000890183.1		c.562G>A	p.Ala188Thr	missense	Exon 6 of 7	ENSP00000560242.1
	RBPMS2	ENST00000890184.1		c.562G>A	p.Ala188Thr	missense	Exon 6 of 8	ENSP00000560243.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000200 AC: 50 AN: 250502 AF XY: 0.000222

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000114 AC: 166 AN: 1461512 Hom.: 0 Cov.: 31 AF XY: 0.000127 AC XY: 92 AN XY: 727046

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.000246 AC: 11 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39686

South Asian (SAS) AF: 0.000568 AC: 49 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.0000782 AC: 87 AN: 1111910

Other (OTH) AF: 0.0000994 AC: 6 AN: 60378

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74474

African (AFR) AF: 0.0000962 AC: 4 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000970 Hom.: 0

Bravo AF: 0.0000831

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000189 AC: 23

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.033
Sift	Benign	0.080	T
Sift4G	Uncertain	0.050	T
Polyphen		0.52	P
Vest4		0.51
MVP		0.29
MPC		0.42
ClinPred		0.026	T
GERP RS		3.6
Varity_R		0.087
gMVP		0.75
Mutation Taster		=59/41	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: rs141658779; hg19: chr15-65040623; COSMIC: COSV105174914;