9-36191205-A-T

Variant names:

• chr9-36191205-A-T
• rs1444661883
• NM_001833.4:c.149A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001833.4(CLTA):​c.149A>T​(p.Glu50Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000565 in 1,416,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (1 hom.)
• Consequence: CLTA NM_001833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3012573).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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.149A>T	p.Glu50Val	missense	Exon 1 of 5	NP_001824.1	P09496-2
	CLTA	NM_007096.4		c.149A>T	p.Glu50Val	missense	Exon 1 of 7	NP_009027.1	P09496-1
	CLTA	NM_001076677.3		c.149A>T	p.Glu50Val	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.149A>T	p.Glu50Val	missense	Exon 1 of 5	ENSP00000242284.6	P09496-2
	CLTA	ENST00000242285.11	TSL:1	c.149A>T	p.Glu50Val	missense	Exon 1 of 7	ENSP00000242285.6	P09496-1
	CLTA	ENST00000396603.6	TSL:1	c.149A>T	p.Glu50Val	missense	Exon 1 of 6	ENSP00000379848.2	P09496-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 168364 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000565 AC: 8 AN: 1416664 Hom.: 1 Cov.: 31 AF XY: 0.00000998 AC XY: 7 AN XY: 701462

African (AFR) AF: 0.000156 AC: 5 AN: 32144

American (AMR) AF: 0.00 AC: 0 AN: 38632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25414

East Asian (EAS) AF: 0.00 AC: 0 AN: 36954

South Asian (SAS) AF: 0.00 AC: 0 AN: 81716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4674

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092982

Other (OTH) AF: 0.0000511 AC: 3 AN: 58732

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.6
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.045	D
Polyphen		0.59	P
Vest4		0.23
MutPred		0.57		Loss of solvent accessibility (P = 0.0146)
MVP		0.79
MPC		1.4
ClinPred		0.99	D
GERP RS		5.4
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.69
gMVP		0.55
Mutation Taster		=19/81	disease causing

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: rs1444661883; hg19: chr9-36191202;