Variant chr9-36191108-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001833.4(CLTA):c.52G>A(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 6.9e-7 ( 0 hom. )

Consequence

CLTA
NM_001833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.550

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 made for transcript

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=0.18134707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLTA	NM_001833.4 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	1/5	ENST00000345519.10	NP_001824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLTA	ENST00000345519.10 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	1/5	1	NM_001833.4	ENSP00000242284	A1	P09496-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1446794

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719728

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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

Sep 06, 2022

The c.52G>A (p.A18T) alteration is located in exon 1 (coding exon 1) of the CLTA gene. This alteration results from a G to A substitution at nucleotide position 52, causing the alanine (A) at amino acid position 18 to be replaced by a threonine (T). 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

0.091

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;.;.;.;T;.;.

Eigen

Benign

0.078

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

D;D;D;D;.;.;D;D

M_CAP

Benign

0.0055

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L;L;L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.73

N;N;N;N;N;N;N;N

REVEL

Benign

0.086

Sift

Uncertain

0.023

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.053

T;D;D;D;D;D;D;D

Polyphen

0.84, 0.82, 0.91

.;P;.;P;.;P;.;P

Vest4

0.25

MutPred

0.36

Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);Gain of glycosylation at A18 (P = 0.0038);

MVP

0.39

MPC

1.4

ClinPred

0.88

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over