X-134244867-C-G

Variant names:

• chrX-134244867-C-G
• rs370691264
• NM_001353453.3:c.67C>G

Variant summary

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

The NM_001353453.3(CCDC160):​c.67C>G​(p.Leu23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,195,369 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: CCDC160 NM_001353453.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499
• Publications: 0 publications found

Genes affected

CCDC160 (HGNC:37286): (coiled-coil domain containing 160)

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=0.0776898).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353453.3. 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
	CCDC160	NM_001353453.3	MANE Select	c.67C>G	p.Leu23Val	missense	Exon 3 of 3	NP_001340382.1	A6NGH7
	CCDC160	NM_001101357.3		c.67C>G	p.Leu23Val	missense	Exon 2 of 2	NP_001094827.1	A6NGH7
	CCDC160	NM_001393996.1		c.67C>G	p.Leu23Val	missense	Exon 3 of 3	NP_001380925.1	A6NGH7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC160	ENST00000695460.1	MANE Select	c.67C>G	p.Leu23Val	missense	Exon 3 of 3	ENSP00000511932.1	A6NGH7
	CCDC160	ENST00000370809.5	TSL:5	c.67C>G	p.Leu23Val	missense	Exon 2 of 2	ENSP00000359845.4	A6NGH7
	CCDC160	ENST00000517294.5	TSL:5	c.67C>G	p.Leu23Val	missense	Exon 3 of 3	ENSP00000427951.1	A6NGH7

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111817 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000650

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

GnomAD2 exomes AF: 0.0000193 AC: 3 AN: 155122 AF XY: 0.00

Gnomad AFR exome AF: 0.000271

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: 9.23e-7 AC: 1 AN: 1083552 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 351800

African (AFR) AF: 0.0000383 AC: 1 AN: 26101

American (AMR) AF: 0.00 AC: 0 AN: 33428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19037

East Asian (EAS) AF: 0.00 AC: 0 AN: 29981

South Asian (SAS) AF: 0.00 AC: 0 AN: 50854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39965

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4107

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834475

Other (OTH) AF: 0.00 AC: 0 AN: 45604

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111817 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34065

African (AFR) AF: 0.0000650 AC: 2 AN: 30767

American (AMR) AF: 0.00 AC: 0 AN: 10458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3589

South Asian (SAS) AF: 0.00 AC: 0 AN: 2700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6041

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53191

Other (OTH) AF: 0.00 AC: 0 AN: 1498

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.000326 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000832 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.94
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.50
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.037
Sift	Benign	0.15	T
Sift4G	Benign	0.23	T
Polyphen		0.57	P
Vest4		0.19
MVP		0.13
MPC		0.0039
ClinPred		0.048	T
GERP RS		2.7
Varity_R		0.13
gMVP		0.023
Mutation Taster		=98/2	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: rs370691264; hg19: chrX-133378897;