chr3-158122114-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001271838.2(RSRC1):c.10C>T(p.Arg4Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000014 in 1,498,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R4Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RSRC1
NM_001271838.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Publications

0 publications found

Variant links:

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]

RSRC1 Gene-Disease associations (from GenCC):

intellectual developmental disorder, autosomal recessive 70
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

RSRC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000134 (18/1346654) while in subpopulation MID AF = 0.00113 (6/5294). AF 95% confidence interval is 0.000493. There are 0 homozygotes in GnomAdExome4. There are 10 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2 link	c.10C>T	p.Arg4Trp	missense_variant	Exon 2 of 10	ENST00000611884.5	NP_001258767.1	Q96IZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSRC1	ENST00000611884.5 link	c.10C>T	p.Arg4Trp	missense_variant	Exon 2 of 10	5	NM_001271838.2	ENSP00000481697.1		Q96IZ7-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000536

AC:

AN:

186672

AF XY:

0.00

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1346654

Hom.:

Cov.:

AF XY:

0.0000150

AC XY:

AN XY:

667412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28146

American (AMR)

AF:

0.00

AC:

AN:

29268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22356

East Asian (EAS)

AF:

0.00

AC:

AN:

34456

South Asian (SAS)

AF:

0.0000304

AC:

AN:

65706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49796

Middle Eastern (MID)

AF:

0.00113

AC:

AN:

5294

European-Non Finnish (NFE)

AF:

0.00000662

AC:

AN:

1056940

Other (OTH)

AF:

0.0000549

AC:

AN:

54692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.10C>T (p.R4W) alteration is located in exon 2 (coding exon 1) of the RSRC1 gene. This alteration results from a C to T substitution at nucleotide position 10, causing the arginine (R) at amino acid position 4 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

0.31

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;T;T;T;.;.;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

.;D;D;.;D;.;T;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.6

L;.;L;L;.;L;L;.;.

PhyloP100

4.0

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.0

D;D;.;D;D;D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D;.;D;D;D;D;D;D

Sift4G

Benign

0.071

T;D;T;T;T;T;T;T;T

Polyphen

1.0

D;.;D;D;.;D;D;.;.

Vest4

0.61

MutPred

0.31

Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);Gain of glycosylation at S5 (P = 0);

MVP

0.91

MPC

0.077

ClinPred

0.92

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.38

gMVP

0.26

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr3-158122114-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over