Variant rs1209338205 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2

The NM_004859.4(CLTC):c.4G>A(p.Ala2Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,868 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.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CLTC
NM_004859.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.54

Variant links:

Genes affected

CLTC (HGNC:2092): (clathrin heavy chain) Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles are involved in the intracellular trafficking of receptors and endocytosis of a variety of macromolecules. The basic subunit of the clathrin coat is composed of three heavy chains and three light chains. [provided by RefSeq, Jul 2008]

CLTC links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM1

In a modified_residue N-acetylalanine (size 0) in uniprot entity CLH1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.3873093).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLTC	NM_004859.4 link	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 32	ENST00000269122.8	NP_004850.1	Q00610-1
CLTC	NM_001288653.2 link	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 32		NP_001275582.1	A0A087WVQ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLTC	ENST00000269122.8 link	c.4G>A	p.Ala2Thr	missense_variant	Exon 1 of 32	1	NM_004859.4	ENSP00000269122.3		Q00610-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248496

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134690

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727232

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:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.029

T;.;T;T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.92

D;D;D;D;D

M_CAP

Benign

0.0090

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.98

.;L;L;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.0

.;N;N;.;.

REVEL

Benign

0.11

Sift

Benign

0.17

.;T;T;.;.

Sift4G

Benign

0.16

T;T;T;T;T

Polyphen

0.0090, 0.98

.;B;D;.;.

Vest4

0.34

MutPred

0.47

Gain of disorder (P = 0.1819);Gain of disorder (P = 0.1819);Gain of disorder (P = 0.1819);Gain of disorder (P = 0.1819);Gain of disorder (P = 0.1819);

MVP

0.58

MPC

1.9

ClinPred

0.92

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over