Variant 22-19183443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007098.4(CLTCL1):c.4774G>A(p.Val1592Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,660 control chromosomes in the GnomAD database, including 307 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0095 ( 34 hom., cov: 33)

Exomes 𝑓: 0.011 ( 273 hom. )

Consequence

CLTCL1
NM_007098.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00200

Variant links:

Genes affected

CLTCL1 (HGNC:2093): (clathrin heavy chain like 1) This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

CLTCL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023112595).

BP6

Variant 22-19183443-C-T is Benign according to our data. Variant chr22-19183443-C-T is described in ClinVar as [Benign]. Clinvar id is 1262625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLTCL1	NM_007098.4 linkuse as main transcript	c.4774G>A	p.Val1592Met	missense_variant	30/33	ENST00000427926.6	NP_009029.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLTCL1	ENST00000427926.6 linkuse as main transcript	c.4774G>A	p.Val1592Met	missense_variant	30/33	1	NM_007098.4	ENSP00000441158	P1	P53675-1

Frequencies

GnomAD3 genomes

AF:

0.00951

AC:

1447

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00792

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.0689

Gnomad SAS

AF:

0.0542

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00745

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0169

AC:

4207

AN:

248308

Hom.:

106

AF XY:

0.0185

AC XY:

2495

AN XY:

134828

show subpopulations

Gnomad AFR exome

AF:

0.00149

Gnomad AMR exome

AF:

0.00589

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0763

Gnomad SAS exome

AF:

0.0485

Gnomad FIN exome

AF:

0.000835

Gnomad NFE exome

AF:

0.00708

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0114

AC:

16695

AN:

1461328

Hom.:

273

Cov.:

AF XY:

0.0125

AC XY:

9079

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00646

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.0677

Gnomad4 SAS exome

AF:

0.0472

Gnomad4 FIN exome

AF:

0.000829

Gnomad4 NFE exome

AF:

0.00719

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.00947

AC:

1442

AN:

152332

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

774

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.0689

Gnomad4 SAS

AF:

0.0536

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00745

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00467

Hom.:

Bravo

AF:

0.00910

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.000930

AC:

ESP6500EA

AF:

0.00814

AC:

ExAC

AF:

0.0166

AC:

2013

EpiCase

AF:

0.00883

EpiControl

AF:

0.00883

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30448225) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.011

DANN

Benign

0.42

DEOGEN2

Benign

0.051

.;T;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.76

T;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.6

.;N;.;.

MutationTaster

Benign

0.69

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

1.2

.;N;.;.

REVEL

Benign

0.034

Sift

Benign

0.47

.;T;.;.

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.0020

B;B;.;.

Vest4

0.096

ClinPred

0.00044

GERP RS

-6.2

Varity_R

0.023

gMVP

0.28

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