chr11-34052539-A-T

Position:

• chr11-34052539-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000341394.9(CAPRIN1):​c.119A>T​(p.Gln40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: CAPRIN1 ENST00000341394.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

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]

LOC101929918 (HGNC:):

ACMG classification

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=0.19773641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPRIN1	NM_005898.5	c.119A>T	p.Gln40Leu	missense_variant	2/19	ENST00000341394.9	NP_005889.3
LOC101929918	XR_931177.3	n.789T>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9	c.119A>T	p.Gln40Leu	missense_variant	2/19	1	NM_005898.5	ENSP00000340329	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.119A>T (p.Q40L) alteration is located in exon 2 (coding exon 1) of the CAPRIN1 gene. This alteration results from a A to T substitution at nucleotide position 119, causing the glutamine (Q) at amino acid position 40 to be replaced by a leucine (L). 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	0.095
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.73
DEOGEN2	Benign	0.076	T;.;T;T;.
Eigen	Benign	-0.079
Eigen_PC	Benign	-0.069
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.58	.;.;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;.;N;N
MutationTaster	Benign	0.70	D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.27	T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.66	P;P;.;P;P
Vest4		0.52
MutPred		0.15		Loss of solvent accessibility (P = 0.0056);Loss of solvent accessibility (P = 0.0056);Loss of solvent accessibility (P = 0.0056);Loss of solvent accessibility (P = 0.0056);Loss of solvent accessibility (P = 0.0056);
MVP		0.51
MPC		0.74
ClinPred		0.33	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.095
gMVP		0.12

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.

Other links and lift over

hg19: chr11-34074086;