Genetic Variant CCDC110:p.Met557Thr (chr4-185458917-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152775.4(CCDC110):c.1670T>C(p.Met557Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,608,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCDC110
NM_152775.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

CCDC110 (HGNC:28504): (coiled-coil domain containing 110) Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CCDC110 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3054341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4 link	c.1670T>C	p.Met557Thr	missense_variant	Exon 6 of 7	ENST00000307588.8	NP_689988.1	Q8TBZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC110	ENST00000307588.8 link	c.1670T>C	p.Met557Thr	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3	Q8TBZ0-1
CCDC110	ENST00000393540.7 link	c.1559T>C	p.Met520Thr	missense_variant	Exon 5 of 6	1		ENSP00000377172.3	Q8TBZ0-2
CCDC110	ENST00000510617.5 link	c.1670T>C	p.Met557Thr	missense_variant	Exon 6 of 7	5		ENSP00000427246.1	E7EUS2
CCDC110	ENST00000651260.1 link	n.1670T>C		non_coding_transcript_exon_variant	Exon 6 of 8			ENSP00000498373.1	A0A494C037

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247622

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133866

show subpopulations

Gnomad AFR exome

AF:

0.0000618

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1456908

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724582

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151974

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000283

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1670T>C (p.M557T) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a T to C substitution at nucleotide position 1670, causing the methionine (M) at amino acid position 557 to be replaced by a threonine (T). 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

0.22

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.013

.;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;M;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.093

Sift

Uncertain

0.012

D;D;D

Sift4G

Benign

0.45

T;T;T

Polyphen

0.87

P;P;.

Vest4

0.48

MutPred

0.38

.;Loss of catalytic residue at M557 (P = 0.0325);Loss of catalytic residue at M557 (P = 0.0325);

MVP

0.33

MPC

0.27

ClinPred

0.94

GERP RS

4.6

Varity_R

0.65

gMVP

0.27

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