11-34071964-A-G

Variant names:

• chr11-34071964-A-G
• NM_005898.5:c.343A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_005898.5(CAPRIN1):​c.343A>G​(p.Ser115Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAPRIN1 NM_005898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.06

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity CAPR1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31829858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPRIN1	NM_005898.5	c.343A>G	p.Ser115Gly	missense_variant	Exon 4 of 19	ENST00000341394.9	NP_005889.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9	c.343A>G	p.Ser115Gly	missense_variant	Exon 4 of 19	1	NM_005898.5	ENSP00000340329.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.343A>G (p.S115G) alteration is located in exon 4 (coding exon 3) of the CAPRIN1 gene. This alteration results from a A to G substitution at nucleotide position 343, causing the serine (S) at amino acid position 115 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D;.;T;D;.;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.61	.;.;T;T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.32	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;.;M;M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		0.83	P;P;.;P;P;.
Vest4		0.34
MutPred		0.27		Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);Loss of stability (P = 0.0311);.;
MVP		0.32
MPC		0.89
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.63
gMVP		0.11

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: chr11-34093511;