9-36191096-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001833.4(CLTA):c.40C>G(p.Pro14Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CLTA NM_001833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.249

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]

ACMG classification

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=0.13758105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLTA	NM_001833.4	c.40C>G	p.Pro14Ala	missense_variant	1/5	ENST00000345519.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTA	ENST00000345519.10	c.40C>G	p.Pro14Ala	missense_variant	1/5	1	NM_001833.4	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.40C>G (p.P14A) alteration is located in exon 1 (coding exon 1) of the CLTA gene. This alteration results from a C to G substitution at nucleotide position 40, causing the proline (P) at amino acid position 14 to be replaced by an alanine (A). 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	0.047
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	17
Dann	Uncertain	0.99
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.81	T;T;T;T;.;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;L;L;L;L;.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.66	N;N;N;N;N;N;N;N
REVEL	Benign	0.094
Sift	Benign	0.31	T;T;T;T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T;T;T;T
Polyphen		1.0, 0.99, 1.0	.;D;.;D;.;D;.;D
Vest4		0.17
MutPred		0.38		Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);Loss of glycosylation at P14 (P = 0.0867);
MVP		0.56
MPC		0.67
ClinPred		0.69	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr9-36191093;