NM_152775.4:c.2167A>G

Variant names:

• chr4-185458420-T-C
• NM_152775.4:c.2167A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152775.4(CCDC110):​c.2167A>G​(p.Lys723Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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]

ACMG classification

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=0.26304847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.2167A>G	p.Lys723Glu	missense_variant	Exon 6 of 7	ENST00000307588.8	NP_689988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC110	ENST00000307588.8	c.2167A>G	p.Lys723Glu	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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.2167A>G (p.K723E) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a A to G substitution at nucleotide position 2167, causing the lysine (K) at amino acid position 723 to be replaced by a glutamic acid (E). 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	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	.;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.62	N;N;N
REVEL	Benign	0.13
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.48
MutPred		0.13		.;Loss of ubiquitination at K723 (P = 0.0077);Loss of ubiquitination at K723 (P = 0.0077);
MVP		0.42
MPC		0.52
ClinPred		0.85	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.037

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.

Other links and lift over

hg19: chr4-186379574;