chr15-57438318-C-G

Position:

• chr15-57438318-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032866.5(CGNL1):​c.319C>G​(p.Pro107Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CGNL1 NM_032866.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.15

Genes affected

CGNL1 (HGNC:25931): (cingulin like 1) This gene encodes a member of the cingulin family. The encoded protein localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1. Heterozygous chromosomal rearrangements resulting in association of the promoter for this gene with the aromatase gene are a cause of aromatase excess syndrome. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25185502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGNL1	NM_032866.5	c.319C>G	p.Pro107Ala	missense_variant	2/19	ENST00000281282.6	NP_116255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGNL1	ENST00000281282.6	c.319C>G	p.Pro107Ala	missense_variant	2/19	1	NM_032866.5	ENSP00000281282.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.319C>G (p.P107A) alteration is located in exon 2 (coding exon 1) of the CGNL1 gene. This alteration results from a C to G substitution at nucleotide position 319, causing the proline (P) at amino acid position 107 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.012	D
Sift4G	Benign	0.13	T
Polyphen		0.82	P
Vest4		0.35
MutPred		0.18		Loss of glycosylation at P107 (P = 0.0507);
MVP		0.82
MPC		0.045
ClinPred		0.68	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.070
gMVP		0.36

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: chr15-57730516;