Variant 5-151183532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015621.3(CCDC69):c.796G>A(p.Glu266Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,458,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCDC69
NM_015621.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

CCDC69 (HGNC:24487): (coiled-coil domain containing 69) Predicted to enable microtubule binding activity. Involved in spindle midzone assembly. Located in spindle midzone. [provided by Alliance of Genome Resources, Apr 2022]

CCDC69 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC69	NM_015621.3 linkuse as main transcript	c.796G>A	p.Glu266Lys	missense_variant	9/9	ENST00000355417.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC69	ENST00000355417.7 linkuse as main transcript	c.796G>A	p.Glu266Lys	missense_variant	9/9	1	NM_015621.3	P1
CCDC69	ENST00000519448.1 linkuse as main transcript	n.955G>A		non_coding_transcript_exon_variant	2/2	1
CCDC69	ENST00000521308.5 linkuse as main transcript	n.843G>A		non_coding_transcript_exon_variant	8/8	1
CCDC69	ENST00000518189.5 linkuse as main transcript	c.*165G>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242430

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000335

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458346

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724990

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.796G>A (p.E266K) alteration is located in exon 9 (coding exon 9) of the CCDC69 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the glutamic acid (E) at amino acid position 266 to be replaced by a lysine (K). 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

Uncertain

0.52

BayesDel_addAF

Benign

0.0032

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0090

Polyphen

1.0

Vest4

0.77

MutPred

0.38

Loss of loop (P = 0.0022);

MVP

0.18

MPC

0.24

ClinPred

0.97

GERP RS

5.7

Varity_R

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over