rs115510695

Positions:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_001080414.4(CCDC88C):c.4889G>T(p.Arg1630Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,612,202 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1630H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.721

Variant links:

Genes affected

CCDC88C (HGNC:19967): (coiled-coil domain containing 88C) This gene encodes a ubiquitously expressed coiled-coil domain-containing protein that interacts with the dishevelled protein and is a negative regulator of the Wnt signalling pathway. The protein encoded by this gene has a PDZ-domain binding motif in its C-terminus with which it interacts with the dishevelled protein. Dishevelled is a scaffold protein involved in the regulation of the Wnt signaling pathway. The Wnt signaling pathway plays an important role in embryonic development, tissue maintenance, and cancer progression. Mutations in this gene cause autosomal recessive, primary non-syndromic congenital hydrocephalus; a condition characterized by excessive accumulation of cerebrospinal fluid in the ventricles of the brain. [provided by RefSeq, Jan 2013]

CCDC88C links:

CCDC88C (HGNC:):

CCDC88C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6

Variant 14-91278091-C-A is Benign according to our data. Variant chr14-91278091-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2049922.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 linkuse as main transcript	c.4889G>T	p.Arg1630Leu	missense_variant	29/30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8
CCDC88C	XM_011536796.3 linkuse as main transcript	c.4781G>T	p.Arg1594Leu	missense_variant	29/30		XP_011535098.1
CCDC88C	XM_047431418.1 linkuse as main transcript	c.4622G>T	p.Arg1541Leu	missense_variant	26/27		XP_047287374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC88C	ENST00000389857.11 linkuse as main transcript	c.4889G>T	p.Arg1630Leu	missense_variant	29/30	5	NM_001080414.4	ENSP00000374507.6	Q9P219-1
CCDC88C	ENST00000334448.5 linkuse as main transcript	n.701G>T		non_coding_transcript_exon_variant	5/6	1
CCDC88C	ENST00000556726 linkuse as main transcript	c.*723G>T		3_prime_UTR_variant	6/7	5		ENSP00000452406.1	H0YJX5
CCDC88C	ENST00000557455.1 linkuse as main transcript	n.*50G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000478

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460008

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

726214

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

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:

0.000478

Bravo

AF:

0.0000151

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 12, 2022

The c.4889G>T (p.R1630L) alteration is located in exon 29 (coding exon 29) of the CCDC88C gene. This alteration results from a G to T substitution at nucleotide position 4889, causing the arginine (R) at amino acid position 1630 to be replaced by a leucine (L). The CCDC88C c.4889G>T alteration was flagged as a low confidence call in the Genome Aggregation Database (gnomAD). This amino acid position is not well conserved in available vertebrate species. This alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.5

D;N

REVEL

Benign

0.077

Sift

Benign

0.13

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.36

.;B

Vest4

0.53

MutPred

0.24

.;Loss of solvent accessibility (P = 0.0155);

MVP

0.61

MPC

0.22

ClinPred

0.56

GERP RS

3.4

Varity_R

0.098

gMVP

0.24

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