Genetic Variant RSRC1:p.Met1? (chr3-158122107-G-T) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001271838.2(RSRC1):c.3G>T(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RSRC1
NM_001271838.2 start_lost

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.18

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 7 pathogenic variants. Next in-frame start position is after 329 codons. Genomic position: 158544255. Lost 0.980 part of the original CDS.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-158122107-G-T is Pathogenic according to our data. Variant chr3-158122107-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1341492.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSRC1	NM_001271838.2 link	c.3G>T	p.Met1?	start_lost	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.3G>T	p.Met1?	start_lost	Exon 2 of 10	5	NM_001271838.2	ENSP00000481697.1		Q96IZ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

179810

AF XY:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1332258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

659206

African (AFR)

AF:

0.00

AC:

AN:

27696

American (AMR)

AF:

0.00

AC:

AN:

26792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21822

East Asian (EAS)

AF:

0.00

AC:

AN:

34298

South Asian (SAS)

AF:

0.00

AC:

AN:

63522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1049632

Other (OTH)

AF:

0.00

AC:

AN:

54022

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Intellectual developmental disorder, autosomal recessive 70

Pathogenic:1

Feb 14, 2022

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.45

BayesDel_noAF

Pathogenic

0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

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

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

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

M_CAP

Benign

0.084

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.0020

PhyloP100

7.2

PROVEAN

Benign

-1.5

N;D;.;N;D;N;N;N;D

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.013

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

Polyphen

0.91

P;.;P;P;.;P;P;.;.

Vest4

0.92

MutPred

0.99

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

0.85

ClinPred

0.99

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.83

gMVP

0.24

Mutation Taster

=54/146

disease causing

(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