rs727505310

Variant names:

• chr10-110812355-C-A
• NM_001134363.3:c.1958C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-110812355-C-A
• chr10-110812355-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001134363.3(RBM20):​c.1958C>A​(p.Thr653Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T653I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RBM20 NM_001134363.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.26

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 Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a region_of_interest RS (size 27) in uniprot entity RBM20_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_001134363.3
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM20	NM_001134363.3	c.1958C>A	p.Thr653Asn	missense_variant	Exon 9 of 14	ENST00000369519.4	NP_001127835.2
RBM20	XM_017016103.3	c.1793C>A	p.Thr598Asn	missense_variant	Exon 9 of 14		XP_016871592.1
RBM20	XM_017016104.3	c.1574C>A	p.Thr525Asn	missense_variant	Exon 9 of 14		XP_016871593.1
RBM20	XM_047425116.1	c.1574C>A	p.Thr525Asn	missense_variant	Exon 9 of 14		XP_047281072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM20	ENST00000369519.4	c.1958C>A	p.Thr653Asn	missense_variant	Exon 9 of 14	1	NM_001134363.3	ENSP00000358532.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399312 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 690168

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: 9.27e-7

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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.015	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0080	D
Vest4		0.70
MutPred		0.10		Loss of phosphorylation at T653 (P = 0.012);
MVP		0.85
ClinPred		0.99	D
GERP RS		5.4
gMVP		0.49

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: chr10-112572113;