1-25246636-G-A

Position:

• chr1-25246636-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020317.5(RSRP1):​c.328C>T​(p.Arg110Trp) 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. 12/20 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: 33)
• Consequence: RSRP1 NM_020317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.664

Genes affected

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

RSRP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20428851).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSRP1	NM_020317.5	c.328C>T	p.Arg110Trp	missense_variant	2/5	ENST00000243189.12	NP_064713.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSRP1	ENST00000243189.12	c.328C>T	p.Arg110Trp	missense_variant	2/5	1	NM_020317.5	ENSP00000243189.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.328C>T (p.R110W) alteration is located in exon 2 (coding exon 1) of the RSRP1 gene. This alteration results from a C to T substitution at nucleotide position 328, causing the arginine (R) at amino acid position 110 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;.;T
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L;L;.
PROVEAN	Uncertain	-3.0	D;N;D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.30
MutPred		0.22		Loss of methylation at R110 (P = 0.0159);Loss of methylation at R110 (P = 0.0159);Loss of methylation at R110 (P = 0.0159);
MVP		0.41
MPC		0.85
ClinPred		0.80	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.16

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: chr1-25573127; COSMIC: COSV54563379; COSMIC: COSV54563379;