9-97314888-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020893.6(CCDC180):c.737A>C(p.Glu246Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC180 NM_020893.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.45

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC180	NM_020893.6	c.737A>C	p.Glu246Ala	missense_variant	8/37	ENST00000529487.3
SUGT1P4-STRA6LP-CCDC180	NR_036528.1	n.2292A>C		non_coding_transcript_exon_variant	22/51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC180	ENST00000529487.3	c.737A>C	p.Glu246Ala	missense_variant	8/37	1	NM_020893.6	P1
CCDC180	ENST00000494917.6	n.940A>C		non_coding_transcript_exon_variant	9/20	1
CCDC180	ENST00000460482.6	n.1071A>C		non_coding_transcript_exon_variant	9/21	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 09, 2021

The c.869A>C (p.E290A) alteration is located in exon 8 (coding exon 8) of the CCDC180 gene. This alteration results from a A to C substitution at nucleotide position 869, causing the glutamic acid (E) at amino acid position 290 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	22
Dann	Uncertain	0.98
Eigen	Benign	0.14
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	0.96	N;N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.13
Sift	Benign	0.039	D
Sift4G	Uncertain	0.0020	D
Vest4		0.54
MVP		0.41
ClinPred		0.77	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-100077170;