rs772179438

Variant names:

• chr10-110821934-G-A
• rs772179438
• NM_001134363.3:c.3315G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110821934-G-A
• chr10-110821934-G-C
• chr10-110821934-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001134363.3(RBM20):​c.3315G>A​(p.Pro1105Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 1,551,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: RBM20 NM_001134363.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00004032
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: 2.15

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=2.15 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.3315G>A	p.Pro1105Pro	splice_region_variant, synonymous_variant	Exon 11 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.3150G>A	p.Pro1050Pro	splice_region_variant, synonymous_variant	Exon 11 of 14		XP_016871592.1
RBM20	XM_017016104.3	c.2931G>A	p.Pro977Pro	splice_region_variant, synonymous_variant	Exon 11 of 14		XP_016871593.1
RBM20	XM_047425116.1	c.2931G>A	p.Pro977Pro	splice_region_variant, synonymous_variant	Exon 11 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.3315G>A	p.Pro1105Pro	splice_region_variant, synonymous_variant	Exon 11 of 14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000640 AC: 1 AN: 156356 Hom.: 0 AF XY: 0.0000121 AC XY: 1 AN XY: 82874

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000439

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000715 AC: 10 AN: 1399350 Hom.: 0 Cov.: 33 AF XY: 0.0000116 AC XY: 8 AN XY: 690180

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000379

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000463

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated cardiomyopathy 1DD Uncertain:1

Dec 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change affects codon 1105 of the RBM20 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RBM20 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs772179438, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with RBM20-related conditions. ClinVar contains an entry for this variant (Variation ID: 566920). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

not specified Benign:1

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.7
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000040
dbscSNV1_RF	Benign	0.038
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: rs772179438; hg19: chr10-112581692;