Variant 1-169421571-G-A 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_001300969.2(CCDC181):c.860C>T(p.Pro287Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CCDC181
NM_001300969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Variant links:

Genes affected

CCDC181 (HGNC:28051): (coiled-coil domain containing 181) Predicted to enable microtubule binding activity. Predicted to be located in manchette and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

CCDC181 links:

Genome browser will be placed here

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=0.091852605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC181	NM_001300969.2 linkuse as main transcript	c.860C>T	p.Pro287Leu	missense_variant	3/6	ENST00000367806.8	NP_001287898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC181	ENST00000367806.8 linkuse as main transcript	c.860C>T	p.Pro287Leu	missense_variant	3/6	1	NM_001300969.2	ENSP00000356780	A1	Q5TID7-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251308

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000161

AC:

236

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

113

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.000176

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

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

Jan 11, 2023

The c.860C>T (p.P287L) alteration is located in exon 3 (coding exon 2) of the CCDC181 gene. This alteration results from a C to T substitution at nucleotide position 860, causing the proline (P) at amino acid position 287 to be replaced by a leucine (L). 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

0.086

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;.;.;.;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.71

T;.;T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

M;M;M;M;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-2.4

N;N;N;.;D

REVEL

Benign

0.051

Sift

Uncertain

0.022

D;D;D;.;D

Sift4G

Uncertain

0.037

D;D;D;T;D

Polyphen

1.0

D;D;D;B;.

Vest4

0.16

MutPred

0.32

Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);

MVP

0.21

MPC

0.17

ClinPred

0.069

GERP RS

3.3

Varity_R

0.042

gMVP

0.14

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