chr4-185458917-A-C

Variant names:

• chr4-185458917-A-C
• rs780496013
• NM_152775.4:c.1670T>G

Variant summary

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

The NM_152775.4(CCDC110):​c.1670T>G​(p.Met557Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: CCDC110 NM_152775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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.1670T>G	p.Met557Arg	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.1670T>G	p.Met557Arg	missense_variant	Exon 6 of 7	1	NM_152775.4	ENSP00000306776.3
CCDC110	ENST00000393540.7	c.1559T>G	p.Met520Arg	missense_variant	Exon 5 of 6	1		ENSP00000377172.3
CCDC110	ENST00000510617.5	c.1670T>G	p.Met557Arg	missense_variant	Exon 6 of 7	5		ENSP00000427246.1
CCDC110	ENST00000651260.1	n.1670T>G		non_coding_transcript_exon_variant	Exon 6 of 8			ENSP00000498373.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74216

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.029	.;T;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.090
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.58	T;T;T
Polyphen		0.76	P;P;.
Vest4		0.63
MutPred		0.35		.;Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);
MVP		0.30
MPC		0.46
ClinPred		0.90	D
GERP RS		4.6
Varity_R		0.90
gMVP		0.53

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: rs780496013; hg19: chr4-186380071;