rs1290935045

Variant names:

• chr3-112605475-T-A
• NM_199511.3:c.2795A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-112605475-T-A
• chr3-112605475-T-G

Variant summary

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

The NM_199511.3(CCDC80):​c.2795A>T​(p.Asp932Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D932A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC80 NM_199511.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.13

Genes affected

CCDC80 (HGNC:30649): (coiled-coil domain containing 80) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within extracellular matrix organization; positive regulation of cell-substrate adhesion; and response to bacterium. Predicted to be located in extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

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 rank	MANE	Protein	UniProt
CCDC80	NM_199511.3	c.2795A>T	p.Asp932Val	missense_variant	Exon 8 of 8	ENST00000206423.8	NP_955805.1
CCDC80	NM_199512.3	c.2795A>T	p.Asp932Val	missense_variant	Exon 8 of 8		NP_955806.1
CCDC80	XM_047447495.1	c.2828A>T	p.Asp943Val	missense_variant	Exon 7 of 7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC80	ENST00000206423.8	c.2795A>T	p.Asp932Val	missense_variant	Exon 8 of 8	1	NM_199511.3	ENSP00000206423.3
CCDC80	ENST00000439685.6	c.2795A>T	p.Asp932Val	missense_variant	Exon 8 of 8	1		ENSP00000411814.2
CCDC80	ENST00000479368.1	c.629A>T	p.Asp210Val	missense_variant	Exon 3 of 3	2		ENSP00000418188.1
CCDC80	ENST00000461431.1	c.*125A>T		downstream_gene_variant		3		ENSP00000420123.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;D;D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D;D
Sift4G	Pathogenic	0.0010	D;D;.
Polyphen		0.94	P;P;.
Vest4		0.39
MutPred		0.31		Gain of catalytic residue at D932 (P = 0.0118);Gain of catalytic residue at D932 (P = 0.0118);.;
MVP		0.80
MPC		0.81
ClinPred		0.93	D
GERP RS		5.8
Varity_R		0.31
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: 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: chr3-112324322;