rs769829513

Variant names:

• chr1-25245152-C-A
• rs769829513
• ENST00000431849.3:c.670G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-25245152-C-A
• chr1-25245152-C-T

Variant summary

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

The NM_020317.5(RSRP1):​c.670G>T​(p.Glu224*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RSRP1 NM_020317.5 stop_gained, splice_region
• Scores: Splicing: ADA: 0.001238
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 0 publications found

Genes affected

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

ENSG00000284657 (HGNC:):

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_020317.5. 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
	RSRP1	NM_020317.5	MANE Select	c.670G>T	p.Glu224*	stop_gained splice_region	Exon 3 of 5	NP_064713.3
	RSRP1	NM_001321772.2		c.670G>T	p.Glu224*	stop_gained splice_region	Exon 3 of 5	NP_001308701.1	Q9BUV0-1
	RSRP1	NR_135143.2		n.882G>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRP1	ENST00000431849.3	TSL:1	c.670G>T	p.Glu224*	stop_gained	Exon 3 of 3	ENSP00000391510.3	Q9BUV0-2
	RSRP1	ENST00000243189.12	TSL:1 MANE Select	c.670G>T	p.Glu224*	stop_gained splice_region	Exon 3 of 5	ENSP00000243189.7	Q9BUV0-1
	RSRP1	ENST00000568254.5	TSL:1	n.670G>T		splice_region non_coding_transcript_exon	Exon 3 of 5	ENSP00000457195.1	H3BTJ0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	36
DANN	Uncertain	0.98
Eigen	Uncertain	0.40
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.77	D
PhyloP100		0.58
Vest4		0.17
GERP RS		2.3
Mutation Taster		=65/135	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.010		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: rs769829513; hg19: chr1-25571643;