Variant 1-169397291-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001300969.2(CCDC181):c.1316A>T(p.Glu439Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,459,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

CCDC181
NM_001300969.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40345168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC181	NM_001300969.2 linkuse as main transcript	c.1316A>T	p.Glu439Val	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.1316A>T	p.Glu439Val	missense_variant	5/6	1	NM_001300969.2	A1	Q5TID7-1
CCDC181	ENST00000367805.7 linkuse as main transcript	c.1313A>T	p.Glu438Val	missense_variant	5/6	1		P4	Q5TID7-3
CCDC181	ENST00000545005.5 linkuse as main transcript	c.1313A>T	p.Glu438Val	missense_variant	6/7	1		P4	Q5TID7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249384

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134934

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1459352

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726046

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 26, 2022

The c.1313A>T (p.E438V) alteration is located in exon 5 (coding exon 4) of the CCDC181 gene. This alteration results from a A to T substitution at nucleotide position 1313, causing the glutamic acid (E) at amino acid position 438 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Benign

-0.30

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.74

T;.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.6

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.47

MutPred

0.29

Gain of MoRF binding (P = 0.0241);.;.;

MVP

0.38

MPC

0.56

ClinPred

0.99

GERP RS

5.8

Varity_R

0.46

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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