Genetic Variant NM_001271838.2:c.-3+310T>C (chr3-158110533-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001271838.2(RSRC1):c.-3+310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,596 control chromosomes in the GnomAD database, including 7,994 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7974 hom., cov: 33)

Exomes 𝑓: 0.25 ( 20 hom. )

Consequence

RSRC1
NM_001271838.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

9 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271838.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RSRC1	NM_001271838.2	MANE Select	c.-3+310T>C	intron	N/A	NP_001258767.1
RSRC1	NM_016625.4		c.-3+322T>C	intron	N/A	NP_057709.2
RSRC1	NM_001271834.2		c.-3+336T>C	intron	N/A	NP_001258763.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RSRC1	ENST00000611884.5	TSL:5 MANE Select	c.-3+310T>C	intron	N/A	ENSP00000481697.1
RSRC1	ENST00000295930.7	TSL:1	c.-3+322T>C	intron	N/A	ENSP00000295930.3
RSRC1	ENST00000312179.10	TSL:1	c.-3+336T>C	intron	N/A	ENSP00000308671.6

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47397

AN:

151990

Hom.:

7955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.287

GnomAD4 exome

AF:

0.248

AC:

121

AN:

488

Hom.:

Cov.:

AF XY:

0.251

AC XY:

AN XY:

374

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

0.688

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.265

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.212

AC:

AN:

368

Other (OTH)

AF:

0.294

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.312

AC:

47481

AN:

152108

Hom.:

7974

Cov.:

AF XY:

0.317

AC XY:

23543

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.394

AC:

16340

AN:

41472

American (AMR)

AF:

0.330

AC:

5039

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3472

East Asian (EAS)

AF:

0.568

AC:

2934

AN:

5170

South Asian (SAS)

AF:

0.239

AC:

1153

AN:

4818

European-Finnish (FIN)

AF:

0.323

AC:

3421

AN:

10596

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.246

AC:

16741

AN:

67976

Other (OTH)

AF:

0.289

AC:

610

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1684

3367

5051

6734

8418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.247

Hom.:

9348

Bravo

AF:

0.319

Asia WGS

AF:

0.384

AC:

1336

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.26

(source)

DANN

Benign

0.41

PhyloP100

-2.0

PromoterAI

-0.058

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over