9-17135124-C-A

Position:

• chr9-17135124-C-A

Variant summary

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

The NM_017738.4(CNTLN):​c.59C>A​(p.Pro20His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CNTLN NM_017738.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67

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=0.07112342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTLN	NM_017738.4	c.59C>A	p.Pro20His	missense_variant	1/26	ENST00000380647.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTLN	ENST00000380647.8	c.59C>A	p.Pro20His	missense_variant	1/26	1	NM_017738.4	P1
CNTLN	ENST00000380641.4	c.59C>A	p.Pro20His	missense_variant	1/7	2
CNTLN	ENST00000484374.1	n.143C>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454606 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 723028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

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

Feb 09, 2023

The c.59C>A (p.P20H) alteration is located in exon 1 (coding exon 1) of the CNTLN gene. This alteration results from a C to A substitution at nucleotide position 59, causing the proline (P) at amino acid position 20 to be replaced by a histidine (H). 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	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.11	N;N
REVEL	Benign	0.066
Sift	Uncertain	0.019	D;D
Sift4G	Benign	0.16	T;T
Polyphen		0.0060	B;B
Vest4		0.35
MutPred		0.18		Loss of glycosylation at P20 (P = 0.0321);Loss of glycosylation at P20 (P = 0.0321);
MVP		0.040
ClinPred		0.63	D
GERP RS		1.5
gMVP		0.12

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: chr9-17135122;