Variant 19-11350823-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_001080503.3(CCDC159):c.242C>T(p.Thr81Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000043 in 1,396,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

CCDC159
NM_001080503.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.927

Variant links:

Genes affected

CCDC159 (HGNC:26996): (coiled-coil domain containing 159)

CCDC159 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=0.07016054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC159	NM_001080503.3 linkuse as main transcript	c.242C>T	p.Thr81Ile	missense_variant	5/11	ENST00000458408.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC159	ENST00000458408.6 linkuse as main transcript	c.242C>T	p.Thr81Ile	missense_variant	5/11	5	NM_001080503.3	P1	P0C7I6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000430

AC:

AN:

1396590

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

688812

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:

0.00000556

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

Apr 19, 2023

The c.242C>T (p.T81I) alteration is located in exon 5 (coding exon 5) of the CCDC159 gene. This alteration results from a C to T substitution at nucleotide position 242, causing the threonine (T) at amino acid position 81 to be replaced by an isoleucine (I). 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

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.53

.;T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.070

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.96

.;N;.;.;.

REVEL

Benign

0.016

Sift

Benign

0.10

.;T;.;.;.

Sift4G

Uncertain

0.035

D;D;T;T;D

Vest4

0.095

MVP

0.15

MPC

0.10

ClinPred

0.16

GERP RS

-0.65

Varity_R

0.042

gMVP

0.079

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over