chr22-19183580-T-C

Position:

• chr22-19183580-T-C

Variant summary

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

The NM_007098.4(CLTCL1):​c.4637A>G​(p.Asp1546Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLTCL1 NM_007098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.90

Genes affected

CLTCL1 (HGNC:2093): (clathrin heavy chain like 1) This gene is a member of the clathrin heavy chain family and encodes a major protein of the polyhedral coat of coated pits and vesicles. Chromosomal aberrations involving this gene are associated with meningioma, DiGeorge syndrome, and velo-cardio-facial syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

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/exons	MANE	UniProt
CLTCL1	NM_007098.4	c.4637A>G	p.Asp1546Gly	missense_variant	30/33	ENST00000427926.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLTCL1	ENST00000427926.6	c.4637A>G	p.Asp1546Gly	missense_variant	30/33	1	NM_007098.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Jul 09, 2021

The c.4637A>G (p.D1546G) alteration is located in exon 30 (coding exon 30) of the CLTCL1 gene. This alteration results from a A to G substitution at nucleotide position 4637, causing the aspartic acid (D) at amino acid position 1546 to be replaced by a glycine (G). 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	0.17
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T;T;.
Eigen	Benign	0.0071
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.72	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.0	.;M;.;.
MutationTaster	Benign	0.73	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.6	.;D;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.015	.;D;.;.
Sift4G	Uncertain	0.021	D;D;D;D
Polyphen		0.48	P;P;.;.
Vest4		0.64
MutPred		0.45		.;Loss of stability (P = 0.1094);.;.;
MVP		0.44
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.32
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-19171093;