Variant 2-55181604-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_152385.4(CLHC1):c.1147T>A(p.Leu383Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CLHC1
NM_152385.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

CLHC1 (HGNC:26453): (clathrin heavy chain linker domain containing 1)

CLHC1 links:

CLHC1 (HGNC:):

CLHC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLHC1	NM_152385.4 linkuse as main transcript	c.1147T>A	p.Leu383Ile	missense_variant	10/13	ENST00000401408.6	NP_689598.2	Q8NHS4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLHC1	ENST00000401408.6 linkuse as main transcript	c.1147T>A	p.Leu383Ile	missense_variant	10/13	1	NM_152385.4	ENSP00000384869.1		Q8NHS4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249542

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

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

AF:

0.00000274

AC:

AN:

1459996

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jun 12, 2023

The c.1147T>A (p.L383I) alteration is located in exon 10 (coding exon 8) of the CLHC1 gene. This alteration results from a T to A substitution at nucleotide position 1147, causing the leucine (L) at amino acid position 383 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

M;M;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.84

P;P;.

Vest4

0.48

MutPred

0.29

Gain of ubiquitination at K381 (P = 0.0716);Gain of ubiquitination at K381 (P = 0.0716);.;

MVP

0.18

MPC

0.033

ClinPred

0.68

GERP RS

4.7

Varity_R

0.10

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 44

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