Variant 11-32613550-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001008391.4(CCDC73):c.2768G>T(p.Ser923Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,614,104 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 49 hom. )

Consequence

CCDC73
NM_001008391.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.95

Variant links:

Genes affected

CCDC73 (HGNC:23261): (coiled-coil domain containing 73)

CCDC73 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005057037).

BP6

Variant 11-32613550-C-A is Benign according to our data. Variant chr11-32613550-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641708.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC73	NM_001008391.4 linkuse as main transcript	c.2768G>T	p.Ser923Ile	missense_variant	16/18	ENST00000335185.10	NP_001008392.2	Q6ZRK6-1
CCDC73	XM_047427029.1 linkuse as main transcript	c.2768G>T	p.Ser923Ile	missense_variant	21/23		XP_047282985.1
CCDC73	XM_047427030.1 linkuse as main transcript	c.2768G>T	p.Ser923Ile	missense_variant	16/18		XP_047282986.1
CCDC73	XM_047427031.1 linkuse as main transcript	c.2510G>T	p.Ser837Ile	missense_variant	15/17		XP_047282987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC73	ENST00000335185.10 linkuse as main transcript	c.2768G>T	p.Ser923Ile	missense_variant	16/18	2	NM_001008391.4	ENSP00000335325.5		Q6ZRK6-1
CCDC73	ENST00000528333.1 linkuse as main transcript	c.136-10530G>T		intron_variant		3		ENSP00000434365.1		H0YDV2

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

684

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00739

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00487

AC:

1216

AN:

249518

Hom.:

AF XY:

0.00502

AC XY:

679

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.00232

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00239

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00702

AC:

10258

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

5028

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.00230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00221

Gnomad4 FIN exome

AF:

0.00161

Gnomad4 NFE exome

AF:

0.00838

Gnomad4 OTH exome

AF:

0.00541

GnomAD4 genome

AF:

0.00449

AC:

684

AN:

152260

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00740

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00592

Hom.:

Bravo

AF:

0.00475

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00218

AC:

ESP6500EA

AF:

0.00785

AC:

ExAC

AF:

0.00500

AC:

604

EpiCase

AF:

0.00703

EpiControl

AF:

0.00871

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

CCDC73: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.032

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.38

M_CAP

Benign

0.0092

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.95

REVEL

Benign

0.061

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

0.12

Vest4

0.12

MVP

0.048

MPC

0.13

ClinPred

0.015

GERP RS

4.3

Varity_R

0.10

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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