Genetic Variant NM_001271838.2:c.158G>A (chr3-158122262-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001271838.2(RSRC1):c.158G>A(p.Arg53Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000276 in 1,446,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R53T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

RSRC1
NM_001271838.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.19

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3833198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2 link	c.158G>A	p.Arg53Lys	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.158G>A	p.Arg53Lys	missense_variant	Exon 2 of 10	5	NM_001271838.2	ENSP00000481697.1		Q96IZ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1446926

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719780

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32388

American (AMR)

AF:

0.00

AC:

AN:

42952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25776

East Asian (EAS)

AF:

0.00

AC:

AN:

38478

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84488

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1104450

Other (OTH)

AF:

0.00

AC:

AN:

59660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

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

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.75

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

M_CAP

Benign

0.0044

MetaRNN

Benign

0.38

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

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.3

M;.;M;M;.;M;M;.;.

PhyloP100

7.2

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.92

N;N;.;N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Pathogenic

0.0

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

Sift4G

Benign

0.23

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

Polyphen

0.97

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

Vest4

0.50

MutPred

0.27

Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);Gain of glycosylation at S50 (P = 0);

MVP

0.86

MPC

0.075

ClinPred

0.92

GERP RS

5.4

Varity_R

0.53

gMVP

0.35

Mutation Taster

=82/18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over