Genetic Variant NM_152775.4:c.1960G>T (chr4-185458627-C-A) – 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.1960G>T(p.Ala654Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC110
NM_152775.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62

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:

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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=0.26687947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4 link	c.1960G>T	p.Ala654Ser	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.1960G>T	p.Ala654Ser	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3	Q8TBZ0-1
CCDC110	ENST00000393540.7 link	c.1849G>T	p.Ala617Ser	missense_variant	Exon 5 of 6	1		ENSP00000377172.3	Q8TBZ0-2
CCDC110	ENST00000510617.5 link	c.1960G>T	p.Ala654Ser	missense_variant	Exon 6 of 7	5		ENSP00000427246.1	E7EUS2
CCDC110	ENST00000651260.1 link	n.1960G>T		non_coding_transcript_exon_variant	Exon 6 of 8			ENSP00000498373.1	A0A494C037

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724562

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1960G>T (p.A654S) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a G to T substitution at nucleotide position 1960, causing the alanine (A) at amino acid position 654 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

.;T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;M;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.63

N;N;N

REVEL

Benign

0.092

Sift

Benign

0.039

D;D;D

Sift4G

Benign

0.48

T;T;T

Polyphen

0.94

P;P;.

Vest4

0.33

MutPred

0.077

.;Gain of glycosylation at T652 (P = 0.0263);Gain of glycosylation at T652 (P = 0.0263);

MVP

0.42

MPC

0.37

ClinPred

0.76

GERP RS

4.7

Varity_R

0.054

gMVP

0.045

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over