Variant chr5-157787828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014666.4(CLINT1):c.1696C>T(p.Leu566Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CLINT1
NM_014666.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

CLINT1 (HGNC:23186): (clathrin interactor 1) This gene encodes a protein with similarity to the epsin family of endocytic adapter proteins. The encoded protein interacts with clathrin, the adapter protein AP-1 and phosphoinositides. This protein may be involved in the formation of clathrin coated vesicles and trafficking between the trans-Golgi network and endosomes. Mutations in this gene are associated with a susceptibility to schizophrenia and psychotic disorders. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2010]

CLINT1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1674867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLINT1	NM_014666.4 linkuse as main transcript	c.1696C>T	p.Leu566Phe	missense_variant	12/12	ENST00000411809.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLINT1	ENST00000411809.7 linkuse as main transcript	c.1696C>T	p.Leu566Phe	missense_variant	12/12	1	NM_014666.4	A1	Q14677-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248946

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Nov 07, 2023

The c.1750C>T (p.L584F) alteration is located in exon 12 (coding exon 12) of the CLINT1 gene. This alteration results from a C to T substitution at nucleotide position 1750, causing the leucine (L) at amino acid position 584 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

Benign

0.069

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

.;.;T;.

Eigen

Benign

0.043

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

.;D;D;D

M_CAP

Benign

0.0082

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L;.

MutationTaster

Benign

0.96

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.059

Sift

Benign

0.031

D;D;D;D

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.24

.;.;B;.

Vest4

0.30

MutPred

0.27

Gain of phosphorylation at T569 (P = 0.1181);Gain of phosphorylation at T569 (P = 0.1181);Gain of phosphorylation at T569 (P = 0.1181);.;

MVP

0.35

MPC

0.14

ClinPred

0.35

GERP RS

5.7

Varity_R

0.051

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over