chr6-43306253-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_206922.3(CRIP3):​c.461G>T​(p.Cys154Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

CRIP3
NM_206922.3 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37
Variant links:
Genes affected
CRIP3 (HGNC:17751): (cysteine rich protein 3) Predicted to enable metal ion binding activity. Predicted to act upstream of or within T cell proliferation. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CRIP3NM_206922.3 linkuse as main transcriptc.461G>T p.Cys154Phe missense_variant 6/8 ENST00000372569.8 NP_996805.2
CRIP3NM_001366068.1 linkuse as main transcriptc.329G>T p.Cys110Phe missense_variant 5/7 NP_001352997.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CRIP3ENST00000372569.8 linkuse as main transcriptc.461G>T p.Cys154Phe missense_variant 6/81 NM_206922.3 ENSP00000361650 P1Q6Q6R5-3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsSep 15, 2021The c.461G>T (p.C154F) alteration is located in exon 6 (coding exon 6) of the CRIP3 gene. This alteration results from a G to T substitution at nucleotide position 461, causing the cysteine (C) at amino acid position 154 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
0.97
BayesDel_addAF
Pathogenic
0.57
D
BayesDel_noAF
Pathogenic
0.58
CADD
Pathogenic
30
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.95
.;.;D
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Pathogenic
0.41
D
MetaRNN
Pathogenic
0.99
D;D;D
MetaSVM
Uncertain
0.76
D
MutationAssessor
Pathogenic
4.9
H;.;H
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-8.0
D;D;D
REVEL
Pathogenic
0.97
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.97
MutPred
0.97
Gain of MoRF binding (P = 0.0722);.;Gain of MoRF binding (P = 0.0722);
MVP
0.99
MPC
0.68
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.83
gMVP
0.77

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: chr6-43273991; API