Variant chr11-86392745-A-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_001156474.2(CCDC81):c.503A>T(p.Asp168Val) variant causes a missense change. The variant allele was found at a frequency of 0.00002 in 1,551,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CCDC81
NM_001156474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.46

Variant links:

Genes affected

CCDC81 (HGNC:26281): (coiled-coil domain containing 81) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CCDC81 links:

LOC105369421 (HGNC:):

LOC105369421 links:

Genome browser will be placed here

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	Protein	UniProt
CCDC81	NM_001156474.2 linkuse as main transcript	c.503A>T	p.Asp168Val	missense_variant	4/15	ENST00000445632.7	NP_001149946.1	Q6ZN84-1
CCDC81	NM_021827.5 linkuse as main transcript	c.286-2589A>T		intron_variant			NP_068599.3	Q6ZN84-2
LOC105369421	XR_007062826.1 linkuse as main transcript	n.81+3275T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC81	ENST00000445632.7 linkuse as main transcript	c.503A>T	p.Asp168Val	missense_variant	4/15	1	NM_001156474.2	ENSP00000415528.2	Q6ZN84-1
CCDC81	ENST00000354755.5 linkuse as main transcript	c.286-2589A>T		intron_variant		2		ENSP00000346800.1	Q6ZN84-2
CCDC81	ENST00000531271.5 linkuse as main transcript	c.142-2589A>T		intron_variant		3		ENSP00000434959.1	E9PMI9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000455

AC:

AN:

153974

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1399318

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

690172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000232

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000189

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 16, 2023

The c.503A>T (p.D168V) alteration is located in exon 4 (coding exon 4) of the CCDC81 gene. This alteration results from a A to T substitution at nucleotide position 503, causing the aspartic acid (D) at amino acid position 168 to be replaced by a valine (V). 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

0.39

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Benign

0.76

DEOGEN2

Benign

0.12

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.6

REVEL

Uncertain

0.34

Sift

Uncertain

0.0030

Sift4G

Benign

0.083

Polyphen

0.71

Vest4

0.68

MVP

0.48

MPC

0.48

ClinPred

0.48

GERP RS

4.6

Varity_R

0.45

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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