1-25246834-G-A

Position:

• chr1-25246834-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.130C>T​(p.Arg44Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RSRP1 NM_020317.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.482

Genes affected

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

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=0.2172342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSRP1	NM_020317.5	c.130C>T	p.Arg44Trp	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.130C>T	p.Arg44Trp	missense_variant	2/5	1	NM_020317.5	ENSP00000243189	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460880 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726648

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

May 03, 2023

The c.130C>T (p.R44W) 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 130, causing the arginine (R) at amino acid position 44 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	0.15
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.044	T;.;T;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.63	T;T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L;.;.;.
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Pathogenic	-4.9	D;D;D;D;D
REVEL	Benign	0.070
Sift	Pathogenic	0.0	D;D;.;.;.
Sift4G	Uncertain	0.0050	D;D;D;D;.
Polyphen		1.0	D;.;.;.;.
Vest4		0.35
MutPred		0.28		Loss of methylation at R44 (P = 0.016);Loss of methylation at R44 (P = 0.016);Loss of methylation at R44 (P = 0.016);Loss of methylation at R44 (P = 0.016);Loss of methylation at R44 (P = 0.016);
MVP		0.41
MPC		0.85
ClinPred		0.97	D
GERP RS		1.7
Varity_R		0.21
gMVP		0.26

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: chr1-25573325;