9-97312168-G-C

Variant names:

• chr9-97312168-G-C
• rs199951239
• NM_020893.6:c.316G>C

Variant summary

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

The NM_020893.6(CCDC180):​c.316G>C​(p.Ala106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A106T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC180 NM_020893.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020893.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC180	NM_020893.6	MANE Select	c.316G>C	p.Ala106Pro	missense	Exon 4 of 37	NP_065944.3	A0A6E1Y6F7
	CCDC180	NM_001348010.4		c.316G>C	p.Ala106Pro	missense	Exon 5 of 21	NP_001334939.2
	SUGT1P4-STRA6LP-CCDC180	NR_036527.1		n.1871G>C		non_coding_transcript_exon	Exon 18 of 49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC180	ENST00000529487.3	TSL:1 MANE Select	c.316G>C	p.Ala106Pro	missense	Exon 4 of 37	ENSP00000434727.2	A0A6E1Y6F7
	CCDC180	ENST00000494917.6	TSL:1	n.519G>C		non_coding_transcript_exon	Exon 5 of 20
	CCDC180	ENST00000867263.1		c.316G>C	p.Ala106Pro	missense	Exon 5 of 35	ENSP00000537322.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.095
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.99	T
PhyloP100		1.7
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0030	D
Vest4		0.60
MVP		0.58
ClinPred		0.94	D
GERP RS		3.2
Varity_R		0.53
gMVP		0.33
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199951239; hg19: chr9-100074450;