rs150512553

Variant names:

• chr14-91278005-G-A
• rs150512553
• NM_001080414.4:c.4975C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-91278005-G-A
• chr14-91278005-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001080414.4(CCDC88C):​c.4975C>T​(p.Arg1659Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000287 in 1,429,824 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1659Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: CCDC88C NM_001080414.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• hydrocephalus, nonsyndromic, autosomal recessive 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• spinocerebellar ataxia type 40

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080414.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	NM_001080414.4	MANE Select	c.4975C>T	p.Arg1659Trp	missense	Exon 29 of 30	NP_001073883.2
	CCDC88C	NR_189158.1		n.5252C>T		non_coding_transcript_exon	Exon 30 of 31
	CCDC88C	NR_189159.1		n.5547C>T		non_coding_transcript_exon	Exon 30 of 31

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88C	ENST00000389857.11	TSL:5 MANE Select	c.4975C>T	p.Arg1659Trp	missense	Exon 29 of 30	ENSP00000374507.6
	CCDC88C	ENST00000334448.5	TSL:1	n.787C>T		non_coding_transcript_exon	Exon 5 of 6
	CCDC88C	ENST00000556726.5	TSL:5	c.*809C>T		3_prime_UTR	Exon 6 of 7	ENSP00000452406.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000150 AC: 3 AN: 200208 AF XY: 0.00000921

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000230

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 41 AN: 1429824 Hom.: 0 Cov.: 32 AF XY: 0.0000226 AC XY: 16 AN XY: 708060

African (AFR) AF: 0.0000305 AC: 1 AN: 32752

American (AMR) AF: 0.00 AC: 0 AN: 40252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 37850

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82314

European-Finnish (FIN) AF: 0.0000195 AC: 1 AN: 51160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.0000347 AC: 38 AN: 1095198

Other (OTH) AF: 0.00 AC: 0 AN: 59054

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 31

Bravo AF: 0.00000378

ExAC AF: 0.0000416 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.0
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.12
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.27		Loss of phosphorylation at S1662 (P = 0.0603)
MVP		0.80
MPC		0.61
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.14
gMVP		0.30
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs150512553; hg19: chr14-91744349; COSMIC: COSV57796426; COSMIC: COSV57796426;