19-11350930-C-A

Variant names:

• chr19-11350930-C-A
• rs766058193
• NM_001080503.3:c.349C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080503.3(CCDC159):​c.349C>A​(p.Arg117Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R117H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC159 NM_001080503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.669
• Publications: 1 publications found

Genes affected

CCDC159 (HGNC:26996): (coiled-coil domain containing 159)

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=0.108439684).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080503.3. 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
	CCDC159	NM_001080503.3	MANE Select	c.349C>A	p.Arg117Ser	missense	Exon 5 of 11	NP_001073972.2	P0C7I6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC159	ENST00000458408.6	TSL:5 MANE Select	c.349C>A	p.Arg117Ser	missense	Exon 5 of 11	ENSP00000402239.1	P0C7I6-2
	CCDC159	ENST00000853370.1		c.349C>A	p.Arg117Ser	missense	Exon 5 of 11	ENSP00000523429.1
	CCDC159	ENST00000588790.5	TSL:5	c.349C>A	p.Arg117Ser	missense	Exon 7 of 13	ENSP00000468232.1	P0C7I6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1401632 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 691648

African (AFR) AF: 0.00 AC: 0 AN: 31810

American (AMR) AF: 0.00 AC: 0 AN: 35944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25198

East Asian (EAS) AF: 0.00 AC: 0 AN: 36004

South Asian (SAS) AF: 0.00 AC: 0 AN: 79356

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080804

Other (OTH) AF: 0.00 AC: 0 AN: 58132

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.67
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.024
Sift	Benign	0.036	D
Sift4G	Benign	0.070	T
Vest4		0.16
MVP		0.12
MPC		0.12
ClinPred		0.60	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.064
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766058193; hg19: chr19-11461606;