4-185458182-T-A

Variant names:

• chr4-185458182-T-A
• rs780469362
• NM_152775.4:c.2405A>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.2405A>T​(p.Tyr802Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. Y802C) 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: -0.0790
• 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=0.07537916).

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.2405A>T	p.Tyr802Phe	missense	Exon 6 of 7	NP_689988.1	Q8TBZ0-1
	CCDC110	NM_001145411.2		c.2294A>T	p.Tyr765Phe	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.2405A>T	p.Tyr802Phe	missense	Exon 6 of 7	ENSP00000306776.3	Q8TBZ0-1
	CCDC110	ENST00000393540.7	TSL:1	c.2294A>T	p.Tyr765Phe	missense	Exon 5 of 6	ENSP00000377172.3	Q8TBZ0-2
	CCDC110	ENST00000510617.5	TSL:5	c.2405A>T	p.Tyr802Phe	missense	Exon 6 of 7	ENSP00000427246.1	E7EUS2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452094 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722166

African (AFR) AF: 0.00 AC: 0 AN: 32886

American (AMR) AF: 0.00 AC: 0 AN: 41868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 83890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109416

Other (OTH) AF: 0.00 AC: 0 AN: 59952

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.80
DANN	Benign	0.36
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.079
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.039
Sift	Benign	0.090	T
Sift4G	Benign	0.36	T
Polyphen		0.47	P
Vest4		0.26
MutPred		0.42		Gain of glycosylation at Y802 (P = 2e-04)
MVP		0.17
MPC		0.19
ClinPred		0.21	T
GERP RS		-0.095
PromoterAI		-0.0054	Neutral
Varity_R		0.081
gMVP		0.013
Mutation Taster		=99/1	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: rs780469362; hg19: chr4-186379336;