2-164692316-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365672.2(COBLL1):c.3205A>G(p.Ser1069Gly) 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: COBLL1 NM_001365672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

Genes affected

COBLL1 (HGNC:23571): (cordon-bleu WH2 repeat protein like 1) Enables cadherin binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28976595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COBLL1	NM_001365672.2	c.3205A>G	p.Ser1069Gly	missense_variant	13/14	ENST00000652658.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COBLL1	ENST00000652658.2	c.3205A>G	p.Ser1069Gly	missense_variant	13/14		NM_001365672.2	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

May 23, 2023

The c.3319A>G (p.S1107G) alteration is located in exon 13 (coding exon 13) of the COBLL1 gene. This alteration results from a A to G substitution at nucleotide position 3319, causing the serine (S) at amino acid position 1107 to be replaced by a glycine (G). 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	0.089
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M;.;.;.
MutationTaster	Benign	0.76	N;N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.0	N;N;N;.
REVEL	Benign	0.085
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.99	D;.;.;.
Vest4		0.41
MutPred		0.19		Loss of phosphorylation at S1145 (P = 0.0255);.;.;.;
MVP		0.79
MPC		0.29
ClinPred		0.96	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.18

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: chr2-165548826;