Variant 11-86387615-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001156474.2(CCDC81):c.241A>G(p.Met81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCDC81
NM_001156474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.257

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:

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ACMG classification

Classification made for transcript

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=0.08184633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC81	NM_001156474.2 linkuse as main transcript	c.241A>G	p.Met81Val	missense_variant	3/15	ENST00000445632.7	NP_001149946.1
LOC105369421	XR_007062826.1 linkuse as main transcript	n.188+152T>C		intron_variant, non_coding_transcript_variant
CCDC81	NM_021827.5 linkuse as main transcript	c.241A>G	p.Met81Val	missense_variant	3/14		NP_068599.3
LOC105369421	XR_007062825.1 linkuse as main transcript	n.210+152T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC81	ENST00000445632.7 linkuse as main transcript	c.241A>G	p.Met81Val	missense_variant	3/15	1	NM_001156474.2	ENSP00000415528	P1	Q6ZN84-1
CCDC81	ENST00000354755.5 linkuse as main transcript	c.241A>G	p.Met81Val	missense_variant	3/14	2		ENSP00000346800		Q6ZN84-2
CCDC81	ENST00000531271.5 linkuse as main transcript	c.141+1503A>G		intron_variant		3		ENSP00000434959

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251220

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

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:

0.00000411

AC:

AN:

1459620

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726268

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

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

Sep 26, 2023

The c.241A>G (p.M81V) alteration is located in exon 3 (coding exon 3) of the CCDC81 gene. This alteration results from a A to G substitution at nucleotide position 241, causing the methionine (M) at amino acid position 81 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

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.67

DANN

Benign

0.66

DEOGEN2

Benign

0.0056

.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.040

Sift

Benign

0.037

D;D

Sift4G

Uncertain

0.028

D;D

Polyphen

0.95

P;B

Vest4

0.24

MutPred

0.52

Gain of catalytic residue at M81 (P = 0.1172);Gain of catalytic residue at M81 (P = 0.1172);

MVP

0.27

MPC

0.14

ClinPred

0.058

GERP RS

-0.31

Varity_R

0.12

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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