4-185458174-C-G

Variant names:

• chr4-185458174-C-G
• rs147851012
• NM_152775.4:c.2413G>C

Variant summary

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

The NM_152775.4(CCDC110):​c.2413G>C​(p.Glu805Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524

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=0.09620443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.2413G>C	p.Glu805Gln	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.2413G>C	p.Glu805Gln	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000346 AC: 5 AN: 1446828 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 719434

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: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.9
DANN	Benign	0.74
DEOGEN2	Benign	0.0044	.;T;.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.096	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	.;L;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.55	N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.16	T;T;T;T
Sift4G	Pathogenic	0.0	D;T;D;T
Polyphen		0.19	B;B;.;.
Vest4		0.16
MutPred		0.30		.;Gain of glycosylation at Y802 (P = 2e-04);.;Gain of glycosylation at Y802 (P = 2e-04);
MVP		0.41
MPC		0.15
ClinPred		0.12	T
GERP RS		1.8
Varity_R		0.077
gMVP		0.056

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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

Other links and lift over

dbSNP: rs147851012; hg19: chr4-186379328;