NM_006614.4:c.49C>G

Variant names:

• chr3-319825-C-G
• rs2272522
• NM_006614.4:c.49C>G

Variant summary

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

The NM_006614.4(CHL1):​c.49C>G​(p.Leu17Val) 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. L17F) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142
• Publications: 42 publications found

Genes affected

CHL1 (HGNC:1939): (cell adhesion molecule L1 like) The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

CHL1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• partial deletion of the short arm of chromosome 3

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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=0.09681824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHL1	NM_006614.4	c.49C>G	p.Leu17Val	missense_variant	Exon 3 of 28	ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7	c.49C>G	p.Leu17Val	missense_variant	Exon 3 of 28	1	NM_006614.4	ENSP00000256509.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.22
DANN	Benign	0.84
DEOGEN2	Benign	0.045	.;T;.;.;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.74	T;T;T;T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.097	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.20	N;N;N;N;N;N;.
REVEL	Benign	0.069
Sift	Benign	0.081	T;T;T;T;T;T;.
Sift4G	Benign	0.10	T;T;T;T;D;T;T
Polyphen		0.043	B;B;.;.;.;.;.
Vest4		0.17
MutPred		0.45		Loss of ubiquitination at K20 (P = 0.1079);Loss of ubiquitination at K20 (P = 0.1079);Loss of ubiquitination at K20 (P = 0.1079);Loss of ubiquitination at K20 (P = 0.1079);Loss of ubiquitination at K20 (P = 0.1079);Loss of ubiquitination at K20 (P = 0.1079);Loss of ubiquitination at K20 (P = 0.1079);
MVP		0.24
MPC		0.012
ClinPred		0.13	T
GERP RS		-2.0
PromoterAI		0.028	Neutral
Varity_R		0.042
gMVP		0.42
Mutation Taster		=98/2	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: rs2272522; hg19: chr3-361508;