10-110644585-C-T

Variant names:

• chr10-110644585-C-T
• NM_001134363.3:c.131C>T

Variant summary

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

The NM_001134363.3(RBM20):​c.131C>T​(p.Pro44Leu) 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. 13/18 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. P44Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664

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 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=0.0565058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.131C>T	p.Pro44Leu	missense_variant	Exon 1 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.26+1145C>T		intron_variant	Intron 1 of 13		XP_016871592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.131C>T	p.Pro44Leu	missense_variant	Exon 1 of 14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1358456 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 669580

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Benign	0.92
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.26	N
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.81	T
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.22
MutPred		0.21		Loss of glycosylation at P44 (P = 0.0094);
MVP		0.26
ClinPred		0.050	T
GERP RS		0.94
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-112404343;