rs2073738

Variant names:

• chr22-19183443-C-A
• rs2073738
• NM_007098.4:c.4774G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-19183443-C-A
• chr22-19183443-C-G
• chr22-19183443-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007098.4(CLTCL1):​c.4774G>T​(p.Val1592Leu) 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. 15/21 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. V1592M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CLTCL1 NM_007098.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044577003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLTCL1	NM_007098.4	c.4774G>T	p.Val1592Leu	missense_variant	Exon 30 of 33	ENST00000427926.6	NP_009029.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLTCL1	ENST00000427926.6	c.4774G>T	p.Val1592Leu	missense_variant	Exon 30 of 33	1	NM_007098.4	ENSP00000441158.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.21
DANN	Benign	0.44
DEOGEN2	Benign	0.051	.;T;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.045	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.66	.;N;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.070	.;N;.;.
REVEL	Benign	0.014
Sift	Benign	0.41	.;T;.;.
Sift4G	Benign	0.52	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.17
MutPred		0.32		.;Loss of catalytic residue at V1592 (P = 0.0059);.;.;
MVP		0.16
ClinPred		0.17	T
GERP RS		-6.2
Varity_R		0.038
gMVP		0.30

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

LitVar

Other links and lift over

dbSNP: rs2073738; hg19: chr22-19170956;