chr4-185458891-G-C

Variant names:

• chr4-185458891-G-C
• NM_152775.4:c.1696C>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.1696C>G​(p.Arg566Gly) 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)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

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=0.1886901).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.1696C>G	p.Arg566Gly	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.1696C>G	p.Arg566Gly	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3
CCDC110	ENST00000393540.7	c.1585C>G	p.Arg529Gly	missense_variant	Exon 5 of 6	1		ENSP00000377172.3
CCDC110	ENST00000510617.5	c.1696C>G	p.Arg566Gly	missense_variant	Exon 6 of 7	5		ENSP00000427246.1
CCDC110	ENST00000651260.1	n.1696C>G		non_coding_transcript_exon_variant	Exon 6 of 8			ENSP00000498373.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1696C>G (p.R566G) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a C to G substitution at nucleotide position 1696, causing the arginine (R) at amino acid position 566 to be replaced by a glycine (G). 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	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	.;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	D;N;D
REVEL	Benign	0.12
Sift	Uncertain	0.024	D;D;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.95	P;P;.
Vest4		0.41
MutPred		0.28		.;Gain of glycosylation at S568 (P = 0.0112);Gain of glycosylation at S568 (P = 0.0112);
MVP		0.27
MPC		0.38
ClinPred		0.85	D
GERP RS		2.9
Varity_R		0.15
gMVP		0.21

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: chr4-186380045;