Variant 11-119193865-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_001145018.3(CCDC153):c.157C>T(p.Arg53Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,551,316 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 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CCDC153
NM_001145018.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

CCDC153 (HGNC:27446): (dynein regulatory complex subunit 12 homolog) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CCDC153 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=0.10143769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC153	NM_001145018.3 linkuse as main transcript	c.157C>T	p.Arg53Cys	missense_variant	4/7	ENST00000503566.7	NP_001138490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC153	ENST00000503566.7 linkuse as main transcript	c.157C>T	p.Arg53Cys	missense_variant	4/7	5	NM_001145018.3	ENSP00000423567	P1	Q494R4-1
CCDC153	ENST00000415318.2 linkuse as main transcript	c.157C>T	p.Arg53Cys	missense_variant	5/8	5		ENSP00000445431	P1	Q494R4-1
CCDC153	ENST00000375140.7 linkuse as main transcript	n.653C>T		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

154036

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81750

show subpopulations

Gnomad AFR exome

AF:

0.000504

Gnomad AMR exome

AF:

0.0000810

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:

0.0000168

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1399262

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

690146

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.0000560

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:

0.0000111

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.000193

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000410

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

Nov 30, 2021

The c.157C>T (p.R53C) alteration is located in exon 4 (coding exon 3) of the CCDC153 gene. This alteration results from a C to T substitution at nucleotide position 157, causing the arginine (R) at amino acid position 53 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.038

Sift

Benign

0.054

T;T

Sift4G

Benign

0.069

T;T

Polyphen

0.20

B;B

Vest4

0.23

MVP

0.39

MPC

0.26

ClinPred

0.062

GERP RS

3.7

Varity_R

0.095

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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