Variant 3-112605458-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.77

Variant links:

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]

CCDC80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC80	NM_199511.3 linkuse as main transcript	c.2812T>C	p.Tyr938His	missense_variant	8/8	ENST00000206423.8
CCDC80	NM_199512.3 linkuse as main transcript	c.2812T>C	p.Tyr938His	missense_variant	8/8
CCDC80	XM_047447495.1 linkuse as main transcript	c.2845T>C	p.Tyr949His	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC80	ENST00000206423.8 linkuse as main transcript	c.2812T>C	p.Tyr938His	missense_variant	8/8	1	NM_199511.3	P1	Q76M96-1
CCDC80	ENST00000439685.6 linkuse as main transcript	c.2812T>C	p.Tyr938His	missense_variant	8/8	1		P1	Q76M96-1
CCDC80	ENST00000479368.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

791

AN:

152208

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00550

AC XY:

747

AN XY:

135720

show subpopulations

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.:

Cov.:

AF XY:

0.00630

AC XY:

4577

AN XY:

727058

show subpopulations

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.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74484

show subpopulations

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.:

Bravo

AF:

0.00540

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00522

AC:

634

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00823

EpiControl

AF:

0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	CCDC80: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.020

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.93

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.69

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over