Genetic Variant NM_001271838.2:c.170C>A (chr3-158122274-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 13/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.747

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: Uncertain_significance. The variant received 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 rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2 link	c.170C>A	p.Pro57His	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.170C>A	p.Pro57His	missense_variant	Exon 2 of 10	5	NM_001271838.2	ENSP00000481697.1		Q96IZ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1436132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714528

African (AFR)

AF:

0.00

AC:

AN:

31762

American (AMR)

AF:

0.00

AC:

AN:

41150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25418

East Asian (EAS)

AF:

0.00

AC:

AN:

37966

South Asian (SAS)

AF:

0.00

AC:

AN:

82650

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099682

Other (OTH)

AF:

0.00

AC:

AN:

59112

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

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

LIST_S2

Benign

0.70

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

M_CAP

Benign

0.0022

MetaRNN

Benign

0.15

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

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

PhyloP100

0.75

PrimateAI

Uncertain

0.52

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

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.23

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over