1-25246942-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020317.5(RSRP1):c.22A>T(p.Met8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 1,433,408 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: RSRP1 NM_020317.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.128

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06556067).
• BP6: Variant 1-25246942-T-A is Benign according to our data. Variant chr1-25246942-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2523150.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRP1	NM_020317.5	c.22A>T	p.Met8Leu	missense_variant	2/5	ENST00000243189.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRP1	ENST00000243189.12	c.22A>T	p.Met8Leu	missense_variant	2/5	1	NM_020317.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000430 AC: 1 AN: 232304 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 127430

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000956

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000907 AC: 13 AN: 1433408 Hom.: 0 Cov.: 31 AF XY: 0.00000987 AC XY: 7 AN XY: 709452

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000365

Gnomad4 OTH exome AF: 0.0000340

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	9.4
Dann	Benign	0.92
DEOGEN2	Benign	0.015	T;.;T;T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.32	T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.066	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.62	N;N;.;.;.
MutationTaster	Benign	1.0	D;N;N
PROVEAN	Benign	-1.3	N;N;D;D;D
REVEL	Benign	0.091
Sift	Pathogenic	0.0	D;D;.;.;.
Sift4G	Benign	1.0	T;T;T;T;.
Polyphen		0.0010	B;.;.;.;.
Vest4		0.19
MutPred		0.19		Loss of MoRF binding (P = 0.1973);Loss of MoRF binding (P = 0.1973);Loss of MoRF binding (P = 0.1973);Loss of MoRF binding (P = 0.1973);Loss of MoRF binding (P = 0.1973);
MVP		0.076
MPC		0.77
ClinPred		0.10	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.70
gMVP		0.21

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

LitVar

Other links and lift over

dbSNP: rs892286700; hg19: chr1-25573433;