chr9-17135289-C-G

Position:

• chr9-17135289-C-G

Variant summary

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

The NM_017738.4(CNTLN):​c.224C>G​(p.Ala75Gly) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNTLN NM_017738.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.654

Genes affected

CNTLN (HGNC:23432): (centlein) Enables protein domain specific binding activity; protein kinase binding activity; and protein-macromolecule adaptor activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in cytosol; microtubule organizing center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15743494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTLN	NM_017738.4	c.224C>G	p.Ala75Gly	missense_variant	1/26	ENST00000380647.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTLN	ENST00000380647.8	c.224C>G	p.Ala75Gly	missense_variant	1/26	1	NM_017738.4	P1
CNTLN	ENST00000380641.4	c.224C>G	p.Ala75Gly	missense_variant	1/7	2
CNTLN	ENST00000484374.1	n.308C>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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 24, 2024

The c.224C>G (p.A75G) alteration is located in exon 1 (coding exon 1) of the CNTLN gene. This alteration results from a C to G substitution at nucleotide position 224, causing the alanine (A) at amino acid position 75 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
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.57	N;N
REVEL	Benign	0.086
Sift	Benign	0.066	T;D
Sift4G	Benign	0.12	T;T
Polyphen		0.83	P;P
Vest4		0.32
MutPred		0.11		Gain of catalytic residue at A75 (P = 0.0347);Gain of catalytic residue at A75 (P = 0.0347);
MVP		0.030
ClinPred		0.86	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.058

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr9-17135287;