Variant 11-34052532-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000341394.9(CAPRIN1):c.112G>A(p.Ala38Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CAPRIN1
ENST00000341394.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

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:

LOC101929918 (HGNC:):

LOC101929918 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12979913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPRIN1	NM_005898.5 linkuse as main transcript	c.112G>A	p.Ala38Thr	missense_variant	2/19	ENST00000341394.9	NP_005889.3
LOC101929918	XR_931177.3 linkuse as main transcript	n.796C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9 linkuse as main transcript	c.112G>A	p.Ala38Thr	missense_variant	2/19	1	NM_005898.5	ENSP00000340329	P2	Q14444-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722748

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2023

The c.112G>A (p.A38T) alteration is located in exon 2 (coding exon 1) of the CAPRIN1 gene. This alteration results from a G to A substitution at nucleotide position 112, causing the alanine (A) at amino acid position 38 to be replaced by a threonine (T). 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

0.078

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.085

T;.;T;T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.72

.;.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.13

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.52

N;N;N;N;N

REVEL

Benign

0.078

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.72

T;T;T;T;T

Polyphen

0.0

B;B;.;B;B

Vest4

0.21

MutPred

0.15

Gain of glycosylation at A38 (P = 0.0017);Gain of glycosylation at A38 (P = 0.0017);Gain of glycosylation at A38 (P = 0.0017);Gain of glycosylation at A38 (P = 0.0017);Gain of glycosylation at A38 (P = 0.0017);

MVP

0.52

MPC

0.73

ClinPred

0.10

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.075

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