11-34076436-C-G

Position:

• chr11-34076436-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005898.5(CAPRIN1):​c.567C>G​(p.Phe189Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CAPRIN1 NM_005898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

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 (HGNC:):

ACMG classification

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, 0.753

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPRIN1	NM_005898.5	c.567C>G	p.Phe189Leu	missense_variant	5/19	ENST00000341394.9	NP_005889.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9	c.567C>G	p.Phe189Leu	missense_variant	5/19	1	NM_005898.5	ENSP00000340329.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461818 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

Gnomad4 AFR exome AF: 0.0000299

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;.;D;.;.
Eigen	Benign	0.012
Eigen_PC	Benign	0.097
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	.;.;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.75	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.19	T;T;T;T;T
Sift4G	Benign	0.070	T;T;T;T;T
Polyphen		0.66	P;P;P;P;.
Vest4		0.80
MutPred		0.73		Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);Gain of disorder (P = 0.0562);.;
MVP		0.92
MPC		0.12
ClinPred		0.98	D
GERP RS		4.8
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.70
gMVP		0.23

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: chr11-34097983;