14-91278091-C-T

Position:

chr14-91278091-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001080414.4(CCDC88C):c.4889G>A(p.Arg1630His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,612,316 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 6 hom. )

Consequence

CCDC88C
NM_001080414.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053323507).

BP6

Variant 14-91278091-C-T is Benign according to our data. Variant chr14-91278091-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 447022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-91278091-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00401 (610/152308) while in subpopulation AFR AF= 0.014 (582/41572). AF 95% confidence interval is 0.0131. There are 3 homozygotes in gnomad4. There are 271 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC88C	NM_001080414.4 linkuse as main transcript	c.4889G>A	p.Arg1630His	missense_variant	29/30	ENST00000389857.11	NP_001073883.2	Q9P219-1B4DZB8
CCDC88C	XM_011536796.3 linkuse as main transcript	c.4781G>A	p.Arg1594His	missense_variant	29/30		XP_011535098.1
CCDC88C	XM_047431418.1 linkuse as main transcript	c.4622G>A	p.Arg1541His	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>A	p.Arg1630His	missense_variant	29/30	5	NM_001080414.4	ENSP00000374507.6	Q9P219-1
CCDC88C	ENST00000334448.5 linkuse as main transcript	n.701G>A		non_coding_transcript_exon_variant	5/6	1
CCDC88C	ENST00000556726 linkuse as main transcript	c.*723G>A		3_prime_UTR_variant	6/7	5		ENSP00000452406.1	H0YJX5
CCDC88C	ENST00000557455.1 linkuse as main transcript	n.*50G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

611

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000441

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000872

AC:

212

AN:

242998

Hom.:

AF XY:

0.000664

AC XY:

AN XY:

132620

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0000880

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:

0.0000364

Gnomad OTH exome

AF:

0.000507

GnomAD4 exome

AF:

0.000395

AC:

576

AN:

1460008

Hom.:

Cov.:

AF XY:

0.000330

AC XY:

240

AN XY:

726214

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000548

GnomAD4 genome

AF:

0.00401

AC:

610

AN:

152308

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000797

Hom.:

Bravo

AF:

0.00454

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00122

AC:

148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 30, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

T;T

Eigen

Benign

0.037

Eigen_PC

Benign

-0.066

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.13

Sift

Benign

0.15

T;T

Sift4G

Benign

0.074

T;T

Polyphen

0.98

.;D

Vest4

0.23

MVP

0.59

MPC

0.17

ClinPred

0.022

GERP RS

3.4

Varity_R

0.033

gMVP

0.20

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