4-185458698-A-G

Variant names:

• chr4-185458698-A-G
• rs2095640121
• NM_152775.4:c.1889T>C

Variant summary

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

The NM_152775.4(CCDC110):​c.1889T>C​(p.Leu630Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.66

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC110	NM_152775.4	c.1889T>C	p.Leu630Pro	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.1889T>C	p.Leu630Pro	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3
CCDC110	ENST00000393540.7	c.1778T>C	p.Leu593Pro	missense_variant	Exon 5 of 6	1		ENSP00000377172.3
CCDC110	ENST00000510617.5	c.1889T>C	p.Leu630Pro	missense_variant	Exon 6 of 7	5		ENSP00000427246.1
CCDC110	ENST00000651260.1	n.1889T>C		non_coding_transcript_exon_variant	Exon 6 of 8			ENSP00000498373.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1889T>C (p.L630P) alteration is located in exon 6 (coding exon 6) of the CCDC110 gene. This alteration results from a T to C substitution at nucleotide position 1889, causing the leucine (L) at amino acid position 630 to be replaced by a proline (P). 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	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	.;T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-4.4	D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.83
MutPred		0.32		.;Loss of stability (P = 0.0129);Loss of stability (P = 0.0129);
MVP		0.49
MPC		0.56
ClinPred		0.96	D
GERP RS		4.3
Varity_R		0.79
gMVP		0.55

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: rs2095640121; hg19: chr4-186379852; COSMIC: COSV100294143; COSMIC: COSV100294143;