3-158122166-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001271838.2(RSRC1):c.62G>A(p.Arg21His) variant causes a missense change. The variant allele was found at a frequency of 0.00181 in 1,597,384 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (4 hom.)
• Consequence: RSRC1 NM_001271838.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.18

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008676797).
• BP6: Variant 3-158122166-G-A is Benign according to our data. Variant chr3-158122166-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041641.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00135 (205/152274) while in subpopulation AMR AF= 0.00353 (54/15292). AF 95% confidence interval is 0.00278. There are 0 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSRC1	NM_001271838.2	c.62G>A	p.Arg21His	missense_variant	2/10	ENST00000611884.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSRC1	ENST00000611884.5	c.62G>A	p.Arg21His	missense_variant	2/10	5	NM_001271838.2	P4

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00156 AC: 374 AN: 239316 Hom.: 2 AF XY: 0.00165 AC XY: 214 AN XY: 129804

Gnomad AFR exome AF: 0.000532

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00112

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00307

Gnomad FIN exome AF: 0.000883

Gnomad NFE exome AF: 0.00181

Gnomad OTH exome AF: 0.00105

GnomAD4 exome AF: 0.00186 AC: 2682 AN: 1445110 Hom.: 4 Cov.: 30 AF XY: 0.00191 AC XY: 1374 AN XY: 718940

Gnomad4 AFR exome AF: 0.000216

Gnomad4 AMR exome AF: 0.00144

Gnomad4 ASJ exome AF: 0.000856

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00265

Gnomad4 FIN exome AF: 0.000717

Gnomad4 NFE exome AF: 0.00203

Gnomad4 OTH exome AF: 0.00143

GnomAD4 genome AF: 0.00135 AC: 205 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.00121 AC XY: 90 AN XY: 74462

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00189 Hom.: 0

Bravo AF: 0.00169

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00208 AC: 8

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00174 AC: 15

ExAC AF: 0.00142 AC: 172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RSRC1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.30
Cadd	Uncertain	24
Dann	Benign	0.96
DEOGEN2	Benign	0.24	T;T;T;T;T;.;.;T;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.0087	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M;.;M;M;.;M;M;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.3	N;D;.;N;D;N;N;N;D
REVEL	Benign	0.19
Sift	Uncertain	0.0070	D;T;.;D;D;T;T;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D;D;D;D;D
Polyphen		0.012	B;.;B;B;.;B;B;.;.
Vest4		0.53
MVP		0.64
MPC		0.092
ClinPred		0.057	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.35

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: rs143641214; hg19: chr3-157839955; COSMIC: COSV55832160;