14-105488235-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001311.5(CRIP1):​c.110C>T​(p.Thr37Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,312 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: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CRIP1
NM_001311.5 missense

Scores

3
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57
Variant links:
Genes affected
CRIP1 (HGNC:2360): (cysteine rich protein 1) Cysteine-rich intestinal protein (CRIP) belongs to the LIM/double zinc finger protein family, members of which include cysteine- and glycine-rich protein-1 (CSRP1; MIM 123876), rhombotin-1 (RBTN1; MIM 186921), rhombotin-2 (RBTN2; MIM 180385), and rhombotin-3 (RBTN3; MIM 180386). CRIP may be involved in intestinal zinc transport (Hempe and Cousins, 1991 [PubMed 1946385]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.858

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRIP1NM_001311.5 linkc.110C>T p.Thr37Met missense_variant Exon 3 of 6 ENST00000392531.4 NP_001302.1 P50238

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRIP1ENST00000392531.4 linkc.110C>T p.Thr37Met missense_variant Exon 3 of 6 2 NM_001311.5 ENSP00000376315.3 P50238
ENSG00000257341ENST00000477724.6 linkn.110C>T non_coding_transcript_exon_variant Exon 2 of 7 4 ENSP00000455329.1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
250314
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135724
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461078
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
726854
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152234
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000727
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.110C>T (p.T37M) alteration is located in exon 3 (coding exon 2) of the CRIP1 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the threonine (T) at amino acid position 37 to be replaced by a methionine (M). 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
0.17
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;T;T
Eigen
Uncertain
0.22
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.88
D
M_CAP
Pathogenic
0.78
D
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Uncertain
0.39
D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-4.2
D;D;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0060
D;D;D
Sift4G
Benign
0.17
T;T;T
Polyphen
0.99
D;D;D
Vest4
0.76
MutPred
0.36
Loss of methylation at K36 (P = 0.0355);Loss of methylation at K36 (P = 0.0355);Loss of methylation at K36 (P = 0.0355);
MVP
0.86
MPC
0.18
ClinPred
0.78
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.41

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781948995; hg19: chr14-105954572; API