3-328247-G-A

Position:

• chr3-328247-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_006614.4(CHL1):​c.278G>A​(p.Arg93Lys) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R93R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHL1 NM_006614.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

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]

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=0.09241268).
• BP6: Variant 3-328247-G-A is Benign according to our data. Variant chr3-328247-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3144390.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4	c.278G>A	p.Arg93Lys	missense_variant	5/28	ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.278G>A	p.Arg93Lys	missense_variant	5/28	1	NM_006614.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.69
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.66	T;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.092	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.63	N;N;N;N;.
REVEL	Benign	0.068
Sift	Benign	1.0	T;T;T;T;.
Sift4G	Benign	0.62	T;T;T;T;T
Polyphen		0.0	B;B;.;.;.
Vest4		0.036
MutPred		0.49		Gain of ubiquitination at R93 (P = 0.0138);Gain of ubiquitination at R93 (P = 0.0138);Gain of ubiquitination at R93 (P = 0.0138);Gain of ubiquitination at R93 (P = 0.0138);Gain of ubiquitination at R93 (P = 0.0138);
MVP		0.45
MPC		0.012
ClinPred		0.071	T
GERP RS		0.91
Varity_R		0.047
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-369930; COSMIC: COSV56608749; COSMIC: COSV56608749;