4-185458999-T-C

Variant names:

• chr4-185458999-T-C
• NM_152775.4:c.1588A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152775.4(CCDC110):​c.1588A>G​(p.Ile530Val) 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. 15/21 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: 0.231

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03877327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.1588A>G	p.Ile530Val	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.1588A>G	p.Ile530Val	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3
CCDC110	ENST00000393540.7	c.1477A>G	p.Ile493Val	missense_variant	Exon 5 of 6	1		ENSP00000377172.3
CCDC110	ENST00000510617.5	c.1588A>G	p.Ile530Val	missense_variant	Exon 6 of 7	5		ENSP00000427246.1
CCDC110	ENST00000651260.1	n.1588A>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

Jan 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1588A>G (p.I530V) 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 1588, causing the isoleucine (I) at amino acid position 530 to be replaced by a valine (V). 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	0.081
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.1
DANN	Benign	0.31
DEOGEN2	Benign	0.0028	.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.21	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.61	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.042
MutPred		0.11		.;Gain of glycosylation at S533 (P = 0.0424);Gain of glycosylation at S533 (P = 0.0424);
MVP		0.040
MPC		0.068
ClinPred		0.091	T
GERP RS		0.25
Varity_R		0.036
gMVP		0.020

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: chr4-186380153;