9-97343500-C-T

Variant names:

• chr9-97343500-C-T
• rs2061634
• NM_020893.6:c.2435C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020893.6(CCDC180):​c.2435C>T​(p.Ser812Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. S812C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC180 NM_020893.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• Publications: 35 publications found

Genes affected

CCDC180 (HGNC:29303): (coiled-coil domain containing 180) The protein encoded by this gene contains a coiled-coil domain. Alternative splicing results in multiple transcript variants encoding different isoforms. A single nucleotide polymorphism (SNP) in this gene has been associated with increased susceptibility to Behcet's Disease (PMID: 19442274). [provided by RefSeq, Dec 2016]

SUGT1P4-STRA6LP-CCDC180 (HGNC:53835): (SUGT1P4-STRA6LP-CCDC180 readthrough) This locus represents a set of read-through transcripts spanning an upstream pseudogene (GeneID:100499484) extending into a downstream protein-coding locus (GeneID:100499483). All of the read-through transcripts are candidates for nonsense-mediated decay (NMD), so they are not thought to express a protein. [provided by RefSeq, Aug 2010]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09076995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC180	NM_020893.6	c.2435C>T	p.Ser812Phe	missense_variant	Exon 19 of 37	ENST00000529487.3	NP_065944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC180	ENST00000529487.3	c.2435C>T	p.Ser812Phe	missense_variant	Exon 19 of 37	1	NM_020893.6	ENSP00000434727.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.72
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.62
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.027
Sift	Benign	0.16	T
Sift4G	Benign	0.29	T
Vest4		0.18
MVP		0.16
ClinPred		0.091	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.070
Mutation Taster		=96/4	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: rs2061634; hg19: chr9-100105782;