chr15-64749042-C-G

Variant names:

• chr15-64749042-C-G
• NM_194272.3:c.376G>C
• RBPMS2 p.Val126Leu

Variant summary

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

The NM_194272.3(RBPMS2):​c.376G>C​(p.Val126Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V126M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBPMS2 NM_194272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• 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: 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=0.02725476).

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.376G>C	p.Val126Leu	missense	Exon 5 of 8	NP_919248.1	Q6ZRY4-1
	RBPMS2	NR_138350.2		n.646G>C		non_coding_transcript_exon	Exon 5 of 8
	RBPMS2	NR_138363.2		n.377G>C		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBPMS2	ENST00000300069.5	TSL:1 MANE Select	c.376G>C	p.Val126Leu	missense	Exon 5 of 8	ENSP00000300069.4	Q6ZRY4-1
	RBPMS2	ENST00000890183.1		c.376G>C	p.Val126Leu	missense	Exon 5 of 7	ENSP00000560242.1
	RBPMS2	ENST00000890184.1		c.376G>C	p.Val126Leu	missense	Exon 5 of 8	ENSP00000560243.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.5
DANN	Benign	0.63
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.0090
Sift	Benign	0.35	T
Sift4G	Benign	0.50	T
Varity_R		0.020
gMVP		0.46

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-65041241;