5-157787818-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014666.4(CLINT1):c.1706C>G(p.Thr569Ser) 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. 15/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05003068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLINT1	NM_014666.4	c.1706C>G	p.Thr569Ser	missense_variant	12/12	ENST00000411809.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLINT1	ENST00000411809.7	c.1706C>G	p.Thr569Ser	missense_variant	12/12	1	NM_014666.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 11, 2022

The c.1760C>G (p.T587S) alteration is located in exon 12 (coding exon 12) of the CLINT1 gene. This alteration results from a C to G substitution at nucleotide position 1760, causing the threonine (T) at amino acid position 587 to be replaced by a serine (S). 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	0.062
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	12
Dann	Benign	0.20
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.050	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.32	N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.64	T;T;T;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.071
MutPred		0.20		Gain of phosphorylation at T569 (P = 0.0987);Gain of phosphorylation at T569 (P = 0.0987);Gain of phosphorylation at T569 (P = 0.0987);.;
MVP		0.18
MPC		0.057
ClinPred		0.019	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.025
gMVP		0.15

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: chr5-157214826;