5-157791840-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014666.4(CLINT1):c.1243C>G(p.Pro415Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CLINT1 NM_014666.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13

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 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=0.12631324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLINT1	NM_014666.4	c.1243C>G	p.Pro415Ala	missense_variant	10/12	ENST00000411809.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLINT1	ENST00000411809.7	c.1243C>G	p.Pro415Ala	missense_variant	10/12	1	NM_014666.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 727132

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: 0.0000261

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

May 11, 2022

The c.1243C>G (p.P415A) alteration is located in exon 10 (coding exon 10) of the CLINT1 gene. This alteration results from a C to G substitution at nucleotide position 1243, causing the proline (P) at amino acid position 415 to be replaced by an alanine (A). 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	0.048
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.2
Dann	Benign	0.76
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	0.67	D;D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.051
Sift	Benign	0.36	T;T;T;T
Sift4G	Benign	0.78	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.25
MutPred		0.18		.;.;Loss of glycosylation at P415 (P = 0.0182);Loss of glycosylation at P415 (P = 0.0182);
MVP		0.38
MPC		0.061
ClinPred		0.060	T
GERP RS		0.39
Varity_R		0.022
gMVP		0.38

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: rs1761920411; hg19: chr5-157218848;