11-34052589-A-T

Variant names:

• chr11-34052589-A-T
• rs1850347042
• NM_005898.5:c.169A>T

Variant summary

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

The NM_005898.5(CAPRIN1):​c.169A>T​(p.Ile57Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,142 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAPRIN1 NM_005898.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPRIN1	NM_005898.5	c.169A>T	p.Ile57Phe	missense_variant	Exon 2 of 19	ENST00000341394.9	NP_005889.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPRIN1	ENST00000341394.9	c.169A>T	p.Ile57Phe	missense_variant	Exon 2 of 19	1	NM_005898.5	ENSP00000340329.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459142 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725748

Gnomad4 AFR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169A>T (p.I57F) 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 169, causing the isoleucine (I) at amino acid position 57 to be replaced by a phenylalanine (F). 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	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;T;T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.95	.;.;D;D;D
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.43	T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.9	L;L;.;L;L
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0080	D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		0.99	D;P;.;D;P
Vest4		0.83
MutPred		0.39		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.89
MPC		1.3
ClinPred		0.86	D
GERP RS		4.2
Varity_R		0.27
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs1850347042; hg19: chr11-34074136;