4-185458627-C-A

Variant names:

• chr4-185458627-C-A
• NM_152775.4:c.1960G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152775.4(CCDC110):​c.1960G>T​(p.Ala654Ser) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26687947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.1960G>T	p.Ala654Ser	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.1960G>T	p.Ala654Ser	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3
CCDC110	ENST00000393540.7	c.1849G>T	p.Ala617Ser	missense_variant	Exon 5 of 6	1		ENSP00000377172.3
CCDC110	ENST00000510617.5	c.1960G>T	p.Ala654Ser	missense_variant	Exon 6 of 7	5		ENSP00000427246.1
CCDC110	ENST00000651260.1	n.1960G>T		non_coding_transcript_exon_variant	Exon 6 of 8			ENSP00000498373.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456242 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 724562

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: 0.00

Gnomad4 OTH exome AF: 0.00

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 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1960G>T (p.A654S) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a G to T substitution at nucleotide position 1960, causing the alanine (A) at amino acid position 654 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	.;T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	.;M;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.63	N;N;N
REVEL	Benign	0.092
Sift	Benign	0.039	D;D;D
Sift4G	Benign	0.48	T;T;T
Polyphen		0.94	P;P;.
Vest4		0.33
MutPred		0.077		.;Gain of glycosylation at T652 (P = 0.0263);Gain of glycosylation at T652 (P = 0.0263);
MVP		0.42
MPC		0.37
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.054
gMVP		0.045

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: chr4-186379781;