rs372188187

Variant names:

• chr4-185458293-C-G
• rs372188187
• NM_152775.4:c.2294G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-185458293-C-G
• chr4-185458293-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152775.4(CCDC110):​c.2294G>C​(p.Arg765Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R765Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19307786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152775.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC110	NM_152775.4	MANE Select	c.2294G>C	p.Arg765Pro	missense	Exon 6 of 7	NP_689988.1	Q8TBZ0-1
	CCDC110	NM_001145411.2		c.2183G>C	p.Arg728Pro	missense	Exon 5 of 6	NP_001138883.1	Q8TBZ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC110	ENST00000307588.8	TSL:1 MANE Select	c.2294G>C	p.Arg765Pro	missense	Exon 6 of 7	ENSP00000306776.3	Q8TBZ0-1
	CCDC110	ENST00000393540.7	TSL:1	c.2183G>C	p.Arg728Pro	missense	Exon 5 of 6	ENSP00000377172.3	Q8TBZ0-2
	CCDC110	ENST00000510617.5	TSL:5	c.2294G>C	p.Arg765Pro	missense	Exon 6 of 7	ENSP00000427246.1	E7EUS2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441530 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 716442

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32120

American (AMR) AF: 0.00 AC: 0 AN: 39214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25256

East Asian (EAS) AF: 0.00 AC: 0 AN: 39264

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81442

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106124

Other (OTH) AF: 0.00 AC: 0 AN: 59460

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.089
Eigen_PC	Benign	0.059
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.32
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.031	D
Polyphen		0.97	D
Vest4		0.70
MutPred		0.16		Loss of disorder (P = 0.2191)
MVP		0.42
MPC		0.47
ClinPred		0.89	D
GERP RS		1.9
PromoterAI		-0.0018	Neutral
Varity_R		0.44
gMVP		0.32
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs372188187; hg19: chr4-186379447;