Genetic Variant CLTCL1:p.Glu1559Asp (chr22-19183540-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007098.4(CLTCL1):c.4677G>C(p.Glu1559Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CLTCL1
NM_007098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.276

Publications

2 publications found

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:

LINC01311 (HGNC:50503): (long intergenic non-protein coding RNA 1311)

LINC01311 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042617857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTCL1	NM_007098.4	MANE Select	c.4677G>C	p.Glu1559Asp	missense	Exon 30 of 33	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.4506G>C	p.Glu1502Asp	missense	Exon 29 of 32	NP_001826.3	P53675-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLTCL1	ENST00000427926.6	TSL:1 MANE Select	c.4677G>C	p.Glu1559Asp	missense	Exon 30 of 33	ENSP00000441158.1	P53675-1
CLTCL1	ENST00000621271.4	TSL:1	c.4506G>C	p.Glu1502Asp	missense	Exon 29 of 32	ENSP00000485020.1	P53675-2
CLTCL1	ENST00000615606.4	TSL:1	n.4770G>C		non_coding_transcript_exon	Exon 29 of 30

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000883

AC:

AN:

249044

AF XY:

0.0000814

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000709

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000160

AC:

234

AN:

1461470

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

125

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000358

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000185

AC:

206

AN:

1111862

Other (OTH)

AF:

0.000116

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41598

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.048

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.73

M_CAP

Benign

0.0049

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.28

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.29

REVEL

Benign

0.052

Sift

Benign

0.66

Sift4G

Benign

0.87

Polyphen

0.0010

Vest4

0.16

MutPred

0.48

Loss of methylation at K1562 (P = 0.0849)

MVP

0.32

ClinPred

0.037

GERP RS

1.9

Varity_R

0.081

gMVP

0.21

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over