Variant 11-34079630-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005898.5(CAPRIN1):c.691A>G(p.Lys231Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CAPRIN1
NM_005898.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.78

Variant links:

Genes affected

CAPRIN1 (HGNC:6743): (cell cycle associated protein 1) Enables RNA binding activity. Predicted to be involved in negative regulation of translation and positive regulation of dendritic spine morphogenesis. Located in cell leading edge and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CAPRIN1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPRIN1	NM_005898.5 link	c.691A>G	p.Lys231Glu	missense_variant, splice_region_variant	Exon 7 of 19	ENST00000341394.9	NP_005889.3	Q14444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9 link	c.691A>G	p.Lys231Glu	missense_variant, splice_region_variant	Exon 7 of 19	1	NM_005898.5	ENSP00000340329.4		Q14444-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460574

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726598

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder

Uncertain:1

Dec 18, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

D;.;D;.;.

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

.;.;T;T;T

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.82

D;D;D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.8

L;L;L;L;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;D

Polyphen

1.0

D;D;D;D;.

Vest4

0.79

MutPred

0.47

Loss of methylation at K231 (P = 0.0067);Loss of methylation at K231 (P = 0.0067);Loss of methylation at K231 (P = 0.0067);Loss of methylation at K231 (P = 0.0067);.;

MVP

0.74

MPC

0.48

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.43

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over