Variant chr1-169397360-C-T 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.1247G>A(p.Arg416Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000048 ( 0 hom. )

Consequence

CCDC181
NM_001300969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0560

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=0.0741134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC181	NM_001300969.2 linkuse as main transcript	c.1247G>A	p.Arg416Gln	missense_variant	5/6	ENST00000367806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC181	ENST00000367806.8 linkuse as main transcript	c.1247G>A	p.Arg416Gln	missense_variant	5/6	1	NM_001300969.2	A1	Q5TID7-1
CCDC181	ENST00000367805.7 linkuse as main transcript	c.1244G>A	p.Arg415Gln	missense_variant	5/6	1		P4	Q5TID7-3
CCDC181	ENST00000545005.5 linkuse as main transcript	c.1244G>A	p.Arg415Gln	missense_variant	6/7	1		P4	Q5TID7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247116

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133724

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1456702

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724730

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:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

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

Aug 29, 2022

The c.1244G>A (p.R415Q) alteration is located in exon 5 (coding exon 4) of the CCDC181 gene. This alteration results from a G to A substitution at nucleotide position 1244, causing the arginine (R) at amino acid position 415 to be replaced by a glutamine (Q). 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

0.084

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0067

T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.75

T;.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;.;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.53

N;N;N

REVEL

Benign

0.0040

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.063

B;B;B

Vest4

0.18

MutPred

0.32

Gain of ubiquitination at K421 (P = 0.0258);.;.;

MVP

0.14

MPC

0.13

ClinPred

0.21

GERP RS

2.7

Varity_R

0.038

gMVP

0.051

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