Variant 11-34076423-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005898.5(CAPRIN1):c.554T>G(p.Leu185Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,870 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CAPRIN1
NM_005898.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

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:

CAPRIN1 (HGNC:):

CAPRIN1 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=0.21905383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPRIN1	NM_005898.5 linkuse as main transcript	c.554T>G	p.Leu185Trp	missense_variant	5/19	ENST00000341394.9	NP_005889.3	Q14444-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9 linkuse as main transcript	c.554T>G	p.Leu185Trp	missense_variant	5/19	1	NM_005898.5	ENSP00000340329.4		Q14444-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

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

May 30, 2024

The c.554T>G (p.L185W) alteration is located in exon 5 (coding exon 4) of the CAPRIN1 gene. This alteration results from a T to G substitution at nucleotide position 554, causing the leucine (L) at amino acid position 185 to be replaced by a tryptophan (W). 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

0.23

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.24

T;.;T;T;.;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

.;.;T;D;D;D

M_CAP

Benign

0.020

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.;L;L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.0

N;N;N;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.15

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.98

D;D;.;D;D;.

Vest4

0.48

MutPred

0.40

Gain of catalytic residue at L183 (P = 0.0039);Gain of catalytic residue at L183 (P = 0.0039);Gain of catalytic residue at L183 (P = 0.0039);Gain of catalytic residue at L183 (P = 0.0039);Gain of catalytic residue at L183 (P = 0.0039);.;

MVP

0.61

MPC

0.28

ClinPred

0.54

GERP RS

4.6

Varity_R

0.10

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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