NM_001833.4:c.305G>C

Variant names:

• chr9-36199028-G-C
• rs10972787
• NM_001833.4:c.305G>C

Variant summary

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

The NM_001833.4(CLTA):​c.305G>C​(p.Arg102Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CLTA NM_001833.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLTA	NM_001833.4	c.305G>C	p.Arg102Pro	missense_variant	Exon 3 of 5	ENST00000345519.10	NP_001824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLTA	ENST00000345519.10	c.305G>C	p.Arg102Pro	missense_variant	Exon 3 of 5	1	NM_001833.4	ENSP00000242284.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;.;.;T;.
Eigen	Benign	0.027
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;.;.;D
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	L;L;L;L;L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	D;D;D;D;D;D
REVEL	Benign	0.26
Sift	Benign	0.32	T;T;T;T;T;T
Sift4G	Benign	0.41	T;T;T;T;T;T
Polyphen		0.0070	B;.;B;.;B;B
Vest4		0.70
MutPred		0.55		Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);
MVP		0.60
MPC		0.78
ClinPred		0.85	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.67
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs10972787; hg19: chr9-36199025;