22-19180775-C-G

Variant names:

• chr22-19180775-C-G
• rs5748024
• NM_007098.4:c.4859G>C

Variant summary

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

The NM_007098.4(CLTCL1):​c.4859G>C​(p.Arg1620Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. R1620C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CLTCL1 NM_007098.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 16 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: 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=0.1544126).

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.4859G>C	p.Arg1620Pro	missense	Exon 31 of 33	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.4688G>C	p.Arg1563Pro	missense	Exon 30 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.4859G>C	p.Arg1620Pro	missense	Exon 31 of 33	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.4688G>C	p.Arg1563Pro	missense	Exon 30 of 32	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.4952G>C		non_coding_transcript_exon	Exon 30 of 30

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	6.8
DANN	Benign	0.91
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.29
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.75	P
Vest4		0.37
MutPred		0.35		Loss of helix (P = 0.0104)
MVP		0.22
ClinPred		0.77	D
GERP RS		-5.8
Varity_R		0.34
gMVP		0.80
Mutation Taster		=91/9	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: rs5748024; hg19: chr22-19168288;