3-158122274-C-A

Variant summary

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

The NM_001271838.2(RSRC1):c.170C>A(p.Pro57His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RSRC1 NM_001271838.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.747

Genes affected

RSRC1 (HGNC:24152): (arginine and serine rich coiled-coil 1) This gene encodes a member of the serine and arginine rich-related protein family. The encoded protein is involved in both constitutive and alternative mRNA splicing. This gene may be associated with schizophrenia. A pseudogene of this gene is located on chromosome 9. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

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=0.14644215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRC1	NM_001271838.2	c.170C>A	p.Pro57His	missense_variant	2/10	ENST00000611884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRC1	ENST00000611884.5	c.170C>A	p.Pro57His	missense_variant	2/10	5	NM_001271838.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1436132 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 714528

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.170C>A (p.P57H) alteration is located in exon 2 (coding exon 1) of the RSRC1 gene. This alteration results from a C to A substitution at nucleotide position 170, causing the proline (P) at amino acid position 57 to be replaced by a histidine (H). 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	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T;T;T;.;.;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.031
FATHMM_MKL	Benign	0.73	D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L;L;.;L;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.7	N;D;.;N;D;N;N;N;D
REVEL	Benign	0.035
Sift	Benign	0.080	T;T;.;T;T;T;T;T;T
Sift4G	Benign	0.099	T;T;T;T;T;T;T;T;T
Polyphen		0.32	B;.;B;B;.;B;B;.;.
Vest4		0.29
MutPred		0.27		Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);Gain of glycosylation at S52 (P = 4e-04);
MVP		0.82
MPC		0.086
ClinPred		0.74	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.076
gMVP		0.23

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: chr3-157840063;