NM_007098.4:c.4739A>C

Variant names:

• chr22-19183478-T-G
• NM_007098.4:c.4739A>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_007098.4(CLTCL1):​c.4739A>C​(p.Asp1580Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 4.00
• Publications: 0 publications found

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]

LINC01311 (HGNC:50503): (long intergenic non-protein coding RNA 1311)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.961

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007098.4. 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
	CLTCL1	NM_007098.4	MANE Select	c.4739A>C	p.Asp1580Ala	missense	Exon 30 of 33	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.4568A>C	p.Asp1523Ala	missense	Exon 29 of 32	NP_001826.3	P53675-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLTCL1	ENST00000427926.6	TSL:1 MANE Select	c.4739A>C	p.Asp1580Ala	missense	Exon 30 of 33	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.4568A>C	p.Asp1523Ala	missense	Exon 29 of 32	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.4832A>C		non_coding_transcript_exon	Exon 29 of 30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.23
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		4.0
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.72		Loss of solvent accessibility (P = 0.1322)
MVP		0.56
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.67
gMVP		0.82
Mutation Taster		=71/29	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

hg19: chr22-19170991;