rs1327164565

Variant names:

• chr1-25245170-T-A
• rs1327164565
• NM_020317.5:c.652A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-25245170-T-A
• chr1-25245170-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020317.5(RSRP1):​c.652A>T​(p.Ser218Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RSRP1 NM_020317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06863403).

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.652A>T	p.Ser218Cys	missense	Exon 3 of 5	NP_064713.3
	RSRP1	NM_001321772.2		c.652A>T	p.Ser218Cys	missense	Exon 3 of 5	NP_001308701.1	Q9BUV0-1
	RSRP1	NR_135143.2		n.864A>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRP1	ENST00000243189.12	TSL:1 MANE Select	c.652A>T	p.Ser218Cys	missense	Exon 3 of 5	ENSP00000243189.7	Q9BUV0-1
	RSRP1	ENST00000431849.3	TSL:1	c.652A>T	p.Ser218Cys	missense	Exon 3 of 3	ENSP00000391510.3	Q9BUV0-2
	RSRP1	ENST00000568254.5	TSL:1	n.652A>T		non_coding_transcript_exon	Exon 3 of 5	ENSP00000457195.1	H3BTJ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251478 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 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: 53418

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.062
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.017
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.040	D
Polyphen		0.010	B
Vest4		0.15
MutPred		0.22		Loss of phosphorylation at S218 (P = 0.0179)
MVP		0.22
MPC		0.026
ClinPred		0.13	T
GERP RS		-0.14
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.32
gMVP		0.11
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1327164565; hg19: chr1-25571661;