Variant 17-82163331-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394669.1(CCDC57):c.1909G>A(p.Gly637Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

CCDC57
NM_001394669.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.339

Variant links:

Genes affected

CCDC57 (HGNC:27564): (coiled-coil domain containing 57) Involved in several processes, including G2/M transition of mitotic cell cycle; cilium assembly; and microtubule cytoskeleton organization. Located in centriolar satellite; centriole; and spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CCDC57 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033911943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC57	NM_001394669.1 linkuse as main transcript	c.1909G>A	p.Gly637Arg	missense_variant	13/19	ENST00000694881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC57	ENST00000694881.1 linkuse as main transcript	c.1909G>A	p.Gly637Arg	missense_variant	13/19		NM_001394669.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

249198

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.000323

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461540

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000790

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.000512

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000496

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Jun 23, 2023

The c.1909G>A (p.G637R) alteration is located in exon 13 (coding exon 12) of the CCDC57 gene. This alteration results from a G to A substitution at nucleotide position 1909, causing the glycine (G) at amino acid position 637 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

0.18

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

Cadd

Benign

8.9

Dann

Benign

0.65

DEOGEN2

Benign

0.0026

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.0010

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.65

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.61

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.52

P;P;B

Vest4

0.19

MutPred

0.24

Gain of MoRF binding (P = 0.0083);Gain of MoRF binding (P = 0.0083);Gain of MoRF binding (P = 0.0083);

MVP

0.32

MPC

0.13

ClinPred

0.015

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.018

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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