19-11350873-C-G

Variant names:

• chr19-11350873-C-G
• rs557635896
• NM_001080503.3:c.292C>G

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.292C>G​(p.Arg98Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,544 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R98P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC159 NM_001080503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• 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=0.13711151).

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.292C>G	p.Arg98Gly	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.292C>G	p.Arg98Gly	missense	Exon 5 of 11	ENSP00000402239.1	P0C7I6-2
	CCDC159	ENST00000853370.1		c.292C>G	p.Arg98Gly	missense	Exon 5 of 11	ENSP00000523429.1
	CCDC159	ENST00000588790.5	TSL:5	c.292C>G	p.Arg98Gly	missense	Exon 7 of 13	ENSP00000468232.1	P0C7I6-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 155088 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399544 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690396

African (AFR) AF: 0.00 AC: 0 AN: 31674

American (AMR) AF: 0.00 AC: 0 AN: 35766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 35878

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5242

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079716

Other (OTH) AF: 0.00 AC: 0 AN: 58038

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.11
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.065
Sift	Benign	0.077	T
Sift4G	Benign	0.11	T
Vest4		0.22
MVP		0.17
MPC		0.23
ClinPred		0.66	D
GERP RS		4.0
Varity_R		0.28
gMVP		0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs557635896; hg19: chr19-11461549;