NM_152775.4:c.2012C>T

Variant names:

• chr4-185458575-G-A
• rs2095639882
• NM_152775.4:c.2012C>T

Variant summary

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

The NM_152775.4(CCDC110):​c.2012C>T​(p.Thr671Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.738

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=0.18605536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.2012C>T	p.Thr671Ile	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.2012C>T	p.Thr671Ile	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1456056 Hom.: 0 Cov.: 34 AF XY: 0.00000690 AC XY: 5 AN XY: 724412

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: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000313 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2012C>T (p.T671I) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a C to T substitution at nucleotide position 2012, causing the threonine (T) at amino acid position 671 to be replaced by an isoleucine (I). 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	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0097	.;T;T
Eigen	Benign	0.092
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.046
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.19	T;T;T
Polyphen		0.92	P;P;.
Vest4		0.40
MutPred		0.15		.;Gain of glycosylation at Y668 (P = 0.0194);Gain of glycosylation at Y668 (P = 0.0194);
MVP		0.39
MPC		0.42
ClinPred		0.53	D
GERP RS		3.7
Varity_R		0.10
gMVP		0.076

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

LitVar

Other links and lift over

dbSNP: rs2095639882; hg19: chr4-186379729;