19-11350828-C-T

Variant names:

• chr19-11350828-C-T
• rs767828537
• NM_001080503.3:c.247C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080503.3(CCDC159):​c.247C>T​(p.Arg83Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,549,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R83H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: CCDC159 NM_001080503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.721
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013745755).

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.247C>T	p.Arg83Cys	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.247C>T	p.Arg83Cys	missense	Exon 5 of 11	ENSP00000402239.1	P0C7I6-2
	CCDC159	ENST00000853370.1		c.247C>T	p.Arg83Cys	missense	Exon 5 of 11	ENSP00000523429.1
	CCDC159	ENST00000588790.5	TSL:5	c.247C>T	p.Arg83Cys	missense	Exon 7 of 13	ENSP00000468232.1	P0C7I6-2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000978 AC: 15 AN: 153424 AF XY: 0.0000982

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000357

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000505

Gnomad OTH exome AF: 0.000232

GnomAD4 exome AF: 0.0000580 AC: 81 AN: 1397274 Hom.: 0 Cov.: 32 AF XY: 0.0000827 AC XY: 57 AN XY: 689174

African (AFR) AF: 0.00 AC: 0 AN: 31624

American (AMR) AF: 0.00 AC: 0 AN: 35634

Ashkenazi Jewish (ASJ) AF: 0.000279 AC: 7 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 35856

South Asian (SAS) AF: 0.000443 AC: 35 AN: 79008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48612

Middle Eastern (MID) AF: 0.000447 AC: 2 AN: 4478

European-Non Finnish (NFE) AF: 0.0000297 AC: 32 AN: 1079062

Other (OTH) AF: 0.0000864 AC: 5 AN: 57896

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152070 Hom.: 0 Cov.: 31 AF XY: 0.0000808 AC XY: 6 AN XY: 74284

African (AFR) AF: 0.000145 AC: 6 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000594 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.72
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.052
Sift	Benign	0.25	T
Sift4G	Benign	0.24	T
Vest4		0.042
MVP		0.18
MPC		0.13
ClinPred		0.031	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.057
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs767828537; hg19: chr19-11461504;