3-112605458-A-G

Position:

• chr3-112605458-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_199511.3(CCDC80):​c.2812T>C​(p.Tyr938His) variant causes a missense change. The variant allele was found at a frequency of 0.00624 in 1,613,834 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (10 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (51 hom.)
• Consequence: CCDC80 NM_199511.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 6.77

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0069583952).
• BP6: Variant 3-112605458-A-G is Benign according to our data. Variant chr3-112605458-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 717696.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC80	NM_199511.3	c.2812T>C	p.Tyr938His	missense_variant	8/8	ENST00000206423.8	NP_955805.1
CCDC80	NM_199512.3	c.2812T>C	p.Tyr938His	missense_variant	8/8		NP_955806.1
CCDC80	XM_047447495.1	c.2845T>C	p.Tyr949His	missense_variant	7/7		XP_047303451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC80	ENST00000206423.8	c.2812T>C	p.Tyr938His	missense_variant	8/8	1	NM_199511.3	ENSP00000206423.3
CCDC80	ENST00000439685.6	c.2812T>C	p.Tyr938His	missense_variant	8/8	1		ENSP00000411814.2
CCDC80	ENST00000479368.1	c.*9T>C		downstream_gene_variant		2		ENSP00000418188.1

Frequencies

GnomAD3 genomes AF: 0.00520 AC: 791 AN: 152208 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00766

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00528 AC: 1326 AN: 251162 Hom.: 12 AF XY: 0.00550 AC XY: 747 AN XY: 135720

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.00327

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00245

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00707

Gnomad OTH exome AF: 0.00752

GnomAD4 exome AF: 0.00635 AC: 9281 AN: 1461508 Hom.: 51 Cov.: 31 AF XY: 0.00630 AC XY: 4577 AN XY: 727058

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.0270

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00250

Gnomad4 FIN exome AF: 0.000449

Gnomad4 NFE exome AF: 0.00693

Gnomad4 OTH exome AF: 0.00654

GnomAD4 genome AF: 0.00519 AC: 791 AN: 152326 Hom.: 10 Cov.: 33 AF XY: 0.00461 AC XY: 343 AN XY: 74484

Gnomad4 AFR AF: 0.00127

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00764

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00801 Hom.: 9

Bravo AF: 0.00540

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00830 AC: 32

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.0100 AC: 86

ExAC AF: 0.00522 AC: 634

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00823

EpiControl AF: 0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	CCDC80: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	.;T
MetaRNN	Benign	0.0070	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.45
MVP		0.88
MPC		0.24
ClinPred		0.043	T
GERP RS		6.0
Varity_R		0.47
gMVP		0.61

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: rs114697626; hg19: chr3-112324305;