Variant 17-82101721-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001394669.1(CCDC57):c.3045G>T(p.Gln1015His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000927 in 1,607,518 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000094 ( 2 hom. )

Consequence

CCDC57
NM_001394669.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.110

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09540343).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC57	NM_001394669.1 linkuse as main transcript	c.3045G>T	p.Gln1015His	missense_variant	19/19	ENST00000694881.1	NP_001381598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC57	ENST00000694881.1 linkuse as main transcript	c.3045G>T	p.Gln1015His	missense_variant	19/19		NM_001394669.1	ENSP00000511565	A2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000123

AC:

AN:

242924

Hom.:

AF XY:

0.000113

AC XY:

AN XY:

132444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.000375

Gnomad NFE exome

AF:

0.000126

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000941

AC:

137

AN:

1455294

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

724032

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000270

Gnomad4 FIN exome

AF:

0.000398

Gnomad4 NFE exome

AF:

0.0000559

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.000108

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 17, 2023

The c.2709G>T (p.Q903H) alteration is located in exon 17 (coding exon 16) of the CCDC57 gene. This alteration results from a G to T substitution at nucleotide position 2709, causing the glutamine (Q) at amino acid position 903 to be replaced by a histidine (H). 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

0.25

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.1

DANN

Benign

0.96

DEOGEN2

Benign

0.0086

T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.48

.;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.095

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.083

Sift

Benign

0.097

T;T

Sift4G

Uncertain

0.030

D;D

Polyphen

0.99

D;D

Vest4

0.16

MutPred

0.14

Loss of glycosylation at P907 (P = 0.1279);Loss of glycosylation at P907 (P = 0.1279);

MVP

0.40

ClinPred

0.040

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

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