rs1253511028

Variant names:

• chr15-64749042-C-A
• rs1253511028
• NM_194272.3:c.376G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-64749042-C-A
• chr15-64749042-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_194272.3(RBPMS2):​c.376G>T​(p.Val126Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RBPMS2 NM_194272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.027362168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBPMS2	NM_194272.3	c.376G>T	p.Val126Leu	missense_variant	Exon 5 of 8	ENST00000300069.5	NP_919248.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBPMS2	ENST00000300069.5	c.376G>T	p.Val126Leu	missense_variant	Exon 5 of 8	1	NM_194272.3	ENSP00000300069.4
RBPMS2	ENST00000560606.5	c.43G>T	p.Val15Leu	missense_variant	Exon 5 of 8	2		ENSP00000456720.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.65
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.027	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.92	N;N
REVEL	Benign	0.0090
Sift	Benign	0.35	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0	.;B
Vest4		0.084
MutPred		0.28		.;Gain of disorder (P = 0.0832);
MVP		0.13
MPC		0.39
ClinPred		0.055	T
GERP RS		-1.9
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

Publications

LitVar

Other links and lift over

dbSNP: rs1253511028; hg19: chr15-65041241;