22-19180793-T-A

Variant names:

• chr22-19180793-T-A
• rs1005433220
• NM_007098.4:c.4841A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007098.4(CLTCL1):​c.4841A>T​(p.Asp1614Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CLTCL1 NM_007098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20
• 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_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13016087).

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.4841A>T	p.Asp1614Val	missense	Exon 31 of 33	NP_009029.3	P53675-1
	CLTCL1	NM_001835.4		c.4670A>T	p.Asp1557Val	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.4841A>T	p.Asp1614Val	missense	Exon 31 of 33	ENSP00000441158.1	P53675-1
	CLTCL1	ENST00000621271.4	TSL:1	c.4670A>T	p.Asp1557Val	missense	Exon 30 of 32	ENSP00000485020.1	P53675-2
	CLTCL1	ENST00000615606.4	TSL:1	n.4934A>T		non_coding_transcript_exon	Exon 30 of 30

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152206 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249182 AF XY: 0.00000740

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461450 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727026

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111778

Other (OTH) AF: 0.0000663 AC: 4 AN: 60358

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152206 Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6 AN XY: 74362

African (AFR) AF: 0.000338 AC: 14 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000128

ClinVar

ClinVar submissions as Germline

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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.88
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.95	L
PhyloP100		3.2
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.061
Sift	Benign	0.052	T
Sift4G	Benign	0.14	T
Polyphen		0.0070	B
Vest4		0.32
MutPred		0.37		Loss of disorder (P = 0.0174)
MVP		0.39
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.093
gMVP		0.62
Mutation Taster		=82/18	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: rs1005433220; hg19: chr22-19168306;