9-97313272-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020893.6(CCDC180):c.386A>G(p.Gln129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,612,104 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: CCDC180 NM_020893.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.737

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.011266708).
• BP6: Variant 9-97313272-A-G is Benign according to our data. Variant chr9-97313272-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2216829.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC180	NM_020893.6	c.386A>G	p.Gln129Arg	missense_variant	5/37	ENST00000529487.3
SUGT1P4-STRA6LP-CCDC180	NR_036528.1	n.1941A>G		non_coding_transcript_exon_variant	19/51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC180	ENST00000529487.3	c.386A>G	p.Gln129Arg	missense_variant	5/37	1	NM_020893.6	P1
CCDC180	ENST00000494917.6	n.589A>G		non_coding_transcript_exon_variant	6/20	1
CCDC180	ENST00000460482.6	n.729A>G		non_coding_transcript_exon_variant	6/21	2

Frequencies

GnomAD3 genomes AF: 0.000638 AC: 97 AN: 152092 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000736 AC: 185 AN: 251434 Hom.: 0 AF XY: 0.000780 AC XY: 106 AN XY: 135894

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.00113 AC: 1649 AN: 1460012 Hom.: 1 Cov.: 30 AF XY: 0.00110 AC XY: 801 AN XY: 726250

Gnomad4 AFR exome AF: 0.0000897

Gnomad4 AMR exome AF: 0.000493

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.00134

Gnomad4 OTH exome AF: 0.000581

GnomAD4 genome AF: 0.000638 AC: 97 AN: 152092 Hom.: 0 Cov.: 32 AF XY: 0.000659 AC XY: 49 AN XY: 74302

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000922 Hom.: 1

Bravo AF: 0.000586

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.000733 AC: 89

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.076
Dann	Benign	0.53
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.022
Sift	Benign	0.67	T
Sift4G	Benign	0.96	T
Vest4		0.045
MVP		0.048
ClinPred		0.0021	T
GERP RS		-11
Varity_R		0.033
gMVP		0.070

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

Other links and lift over

dbSNP: rs140801022; hg19: chr9-100075554;