9-36191096-C-T

Variant names:

• chr9-36191096-C-T
• rs1826674493
• NM_001833.4:c.40C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001833.4(CLTA):​c.40C>T​(p.Pro14Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P14A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CLTA NM_001833.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13774458).

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.40C>T	p.Pro14Ser	missense	Exon 1 of 5	NP_001824.1	P09496-2
	CLTA	NM_007096.4		c.40C>T	p.Pro14Ser	missense	Exon 1 of 7	NP_009027.1	P09496-1
	CLTA	NM_001076677.3		c.40C>T	p.Pro14Ser	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.40C>T	p.Pro14Ser	missense	Exon 1 of 5	ENSP00000242284.6	P09496-2
	CLTA	ENST00000242285.11	TSL:1	c.40C>T	p.Pro14Ser	missense	Exon 1 of 7	ENSP00000242285.6	P09496-1
	CLTA	ENST00000396603.6	TSL:1	c.40C>T	p.Pro14Ser	missense	Exon 1 of 6	ENSP00000379848.2	P09496-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440362 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716596

African (AFR) AF: 0.00 AC: 0 AN: 32062

American (AMR) AF: 0.00 AC: 0 AN: 42362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25512

East Asian (EAS) AF: 0.00 AC: 0 AN: 38360

South Asian (SAS) AF: 0.00 AC: 0 AN: 85022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1106418

Other (OTH) AF: 0.00 AC: 0 AN: 59502

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.25
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.12
Sift	Benign	0.051	T
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.12
MutPred		0.40		Gain of glycosylation at P14 (P = 0.0118)
MVP		0.47
MPC		1.1
ClinPred		0.88	D
GERP RS		3.8
PromoterAI		-0.0068	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.36
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs1826674493; hg19: chr9-36191093;