Genetic Variant CLTA:p.Glu50Gly (chr9-36191205-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001833.4(CLTA):c.149A>G(p.Glu50Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,416,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E50V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CLTA
NM_001833.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.58

Publications

0 publications found

Variant links:

Genes affected

CLTA (HGNC:2090): (clathrin light chain A) Clathrin is a large, soluble protein composed of heavy and light chains. It functions as the main structural component of the lattice-type cytoplasmic face of coated pits and vesicles which entrap specific macromolecules during receptor-mediated endocytosis. This gene encodes one of two clathrin light chain proteins which are believed to function as regulatory elements. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 8 and 12. [provided by RefSeq, May 2010]

CLTA links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28906268).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001833.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLTA	NM_001833.4	MANE Select	c.149A>G	p.Glu50Gly	missense	Exon 1 of 5	NP_001824.1	P09496-2
CLTA	NM_007096.4		c.149A>G	p.Glu50Gly	missense	Exon 1 of 7	NP_009027.1	P09496-1
CLTA	NM_001076677.3		c.149A>G	p.Glu50Gly	missense	Exon 1 of 6	NP_001070145.1	P09496-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLTA	ENST00000345519.10	TSL:1 MANE Select	c.149A>G	p.Glu50Gly	missense	Exon 1 of 5	ENSP00000242284.6	P09496-2
CLTA	ENST00000242285.11	TSL:1	c.149A>G	p.Glu50Gly	missense	Exon 1 of 7	ENSP00000242285.6	P09496-1
CLTA	ENST00000396603.6	TSL:1	c.149A>G	p.Glu50Gly	missense	Exon 1 of 6	ENSP00000379848.2	P09496-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1416664

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32144

American (AMR)

AF:

0.00

AC:

AN:

38632

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25414

East Asian (EAS)

AF:

0.00

AC:

AN:

36954

South Asian (SAS)

AF:

0.00

AC:

AN:

81716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4674

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1092982

Other (OTH)

AF:

0.00

AC:

AN:

58732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.074

MetaRNN

Benign

0.29

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.4

PhyloP100

5.6

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.37

Sift

Uncertain

0.0090

Sift4G

Benign

0.28

Polyphen

0.99

Vest4

0.17

MutPred

0.56

Loss of solvent accessibility (P = 0.0769)

MVP

0.77

MPC

1.4

ClinPred

0.97

GERP RS

5.4

PromoterAI

-0.18

Neutral

(source)

Varity_R

0.61

gMVP

0.48

Mutation Taster

=19/81

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over