rs1027203249

Variant names:

• chr10-110644474-T-C
• rs1027203249
• NM_001134363.3:c.20T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-110644474-T-C
• chr10-110644474-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134363.3(RBM20):​c.20T>C​(p.Met7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M7V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 publications found

Genes affected

RBM20 (HGNC:27424): (RNA binding motif protein 20) This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy. [provided by RefSeq, Apr 2014]

RBM20 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• dilated cardiomyopathy 1DD

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134363.3. 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
	RBM20	NM_001134363.3	MANE Select	c.20T>C	p.Met7Thr	missense	Exon 1 of 14	NP_001127835.2	Q5T481

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM20	ENST00000369519.4	TSL:1 MANE Select	c.20T>C	p.Met7Thr	missense	Exon 1 of 14	ENSP00000358532.3	Q5T481
	RBM20	ENST00000961386.1		c.20T>C	p.Met7Thr	missense	Exon 1 of 14	ENSP00000631445.1
	RBM20	ENST00000718239.1		c.20T>C	p.Met7Thr	missense	Exon 1 of 14	ENSP00000520684.1	Q5T481

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1366524 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674014

African (AFR) AF: 0.00 AC: 0 AN: 28188

American (AMR) AF: 0.00 AC: 0 AN: 33250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24278

East Asian (EAS) AF: 0.00 AC: 0 AN: 32778

South Asian (SAS) AF: 0.00 AC: 0 AN: 76514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4038

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069764

Other (OTH) AF: 0.00 AC: 0 AN: 56702

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	0.039
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.26	T
PhyloP100		1.2
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.61	N
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.21	T
Vest4		0.65
MutPred		0.21		Gain of phosphorylation at M7 (P = 0.0387)
MVP		0.60
ClinPred		0.88	D
GERP RS		4.2
PromoterAI		-0.19	Neutral
gMVP		0.38
Mutation Taster		=93/7	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: rs1027203249; hg19: chr10-112404232;