9-36191208-C-G

Variant names:

• chr9-36191208-C-G
• rs1224331668
• NM_001833.4:c.152C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001833.4(CLTA):​c.152C>G​(p.Ala51Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. A51T) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CLTA NM_001833.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050700337).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTA	NM_001833.4	MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 1 of 5	NP_001824.1	P09496-2
	CLTA	NM_007096.4		c.152C>G	p.Ala51Gly	missense	Exon 1 of 7	NP_009027.1	P09496-1
	CLTA	NM_001076677.3		c.152C>G	p.Ala51Gly	missense	Exon 1 of 6	NP_001070145.1	P09496-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTA	ENST00000345519.10	TSL:1 MANE Select	c.152C>G	p.Ala51Gly	missense	Exon 1 of 5	ENSP00000242284.6	P09496-2
	CLTA	ENST00000242285.11	TSL:1	c.152C>G	p.Ala51Gly	missense	Exon 1 of 7	ENSP00000242285.6	P09496-1
	CLTA	ENST00000396603.6	TSL:1	c.152C>G	p.Ala51Gly	missense	Exon 1 of 6	ENSP00000379848.2	P09496-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.8	N
PhyloP100		4.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	1.7	N
REVEL	Uncertain	0.36
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.55		Loss of stability (P = 0.0303)
MVP		0.13
MPC		0.53
ClinPred		0.48	T
GERP RS		4.5
PromoterAI		-0.34	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.63
gMVP		0.33
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs1224331668; hg19: chr9-36191205;