Variant 12-438542-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032358.4(CCDC77):c.1029T>A(p.Ser343Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC77
NM_032358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.797

Variant links:

Genes affected

CCDC77 (HGNC:28203): (coiled-coil domain containing 77) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

CCDC77 links:

CCDC77 (HGNC:):

CCDC77 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10149655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC77	NM_032358.4 linkuse as main transcript	c.1029T>A	p.Ser343Arg	missense_variant	10/13	ENST00000239830.9	NP_115734.1	Q9BR77-1
CCDC77	NM_001130146.2 linkuse as main transcript	c.933T>A	p.Ser311Arg	missense_variant	9/12		NP_001123618.1	Q9BR77-2
CCDC77	NM_001130147.2 linkuse as main transcript	c.933T>A	p.Ser311Arg	missense_variant	9/12		NP_001123619.1	Q9BR77-2
CCDC77	NM_001130148.2 linkuse as main transcript	c.933T>A	p.Ser311Arg	missense_variant	8/11		NP_001123620.1	Q9BR77-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC77	ENST00000239830.9 linkuse as main transcript	c.1029T>A	p.Ser343Arg	missense_variant	10/13	2	NM_032358.4	ENSP00000239830.4		Q9BR77-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250400

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458512

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725764

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.1029T>A (p.S343R) alteration is located in exon 10 (coding exon 8) of the CCDC77 gene. This alteration results from a T to A substitution at nucleotide position 1029, causing the serine (S) at amino acid position 343 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.021

.;.;T;T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.58

.;T;T;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

.;.;.;N;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.98

N;N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.18

T;T;T;T;T

Sift4G

Benign

0.079

T;T;T;T;T

Polyphen

0.16

.;.;.;B;.

Vest4

0.18

MutPred

0.20

.;.;.;Gain of MoRF binding (P = 0.0137);.;

MVP

0.64

MPC

0.19

ClinPred

0.11

GERP RS

0.85

Varity_R

0.040

gMVP

0.15

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