NM_020317.5:c.716A>T

Variant names:

• chr1-25243590-T-A
• rs1043879
• NM_020317.5:c.716A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020317.5(RSRP1):​c.716A>T​(p.Glu239Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RSRP1 NM_020317.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2845779).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRP1	NM_020317.5	MANE Select	c.716A>T	p.Glu239Val	missense	Exon 4 of 5	NP_064713.3
	RSRP1	NM_001321772.2		c.716A>T	p.Glu239Val	missense	Exon 4 of 5	NP_001308701.1
	RSRP1	NR_135143.2		n.2444A>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSRP1	ENST00000243189.12	TSL:1 MANE Select	c.716A>T	p.Glu239Val	missense	Exon 4 of 5	ENSP00000243189.7
	RSRP1	ENST00000568254.5	TSL:1	n.*626A>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000457195.1
	RSRP1	ENST00000568254.5	TSL:1	n.*626A>T		3_prime_UTR	Exon 4 of 5	ENSP00000457195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461500 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111802

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.013
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.0
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.21	T
Polyphen		0.99	D
Vest4		0.42
MutPred		0.11		Gain of MoRF binding (P = 0.0269)
MVP		0.27
MPC		0.21
ClinPred		0.94	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.41
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1043879; hg19: chr1-25570081;