X-134245748-C-G

Variant names:

• chrX-134245748-C-G
• rs751427720
• NM_001353453.3:c.948C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001353453.3(CCDC160):​c.948C>G​(p.Ile316Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000145 in 1,032,649 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000015 (0 hom. 4 hem.)
• Consequence: CCDC160 NM_001353453.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.367
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13719672).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

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.948C>G	p.Ile316Met	missense	Exon 3 of 3	NP_001340382.1	A6NGH7
	CCDC160	NM_001101357.3		c.948C>G	p.Ile316Met	missense	Exon 2 of 2	NP_001094827.1	A6NGH7
	CCDC160	NM_001393996.1		c.948C>G	p.Ile316Met	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.948C>G	p.Ile316Met	missense	Exon 3 of 3	ENSP00000511932.1	A6NGH7
	CCDC160	ENST00000370809.5	TSL:5	c.948C>G	p.Ile316Met	missense	Exon 2 of 2	ENSP00000359845.4	A6NGH7
	CCDC160	ENST00000517294.5	TSL:5	c.948C>G	p.Ile316Met	missense	Exon 3 of 3	ENSP00000427951.1	A6NGH7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000145 AC: 15 AN: 1032649 Hom.: 0 Cov.: 28 AF XY: 0.0000125 AC XY: 4 AN XY: 321089

African (AFR) AF: 0.00 AC: 0 AN: 23620

American (AMR) AF: 0.00 AC: 0 AN: 21863

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17030

East Asian (EAS) AF: 0.00 AC: 0 AN: 28621

South Asian (SAS) AF: 0.00 AC: 0 AN: 42902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3924

European-Non Finnish (NFE) AF: 0.0000185 AC: 15 AN: 812888

Other (OTH) AF: 0.00 AC: 0 AN: 43327

GnomAD4 genome Cov.: 23

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	0.094
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.3
DANN	Benign	0.56
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.38	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.37
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.21
Sift	Benign	0.050	D
Sift4G	Benign	0.10	T
Polyphen		0.88	P
Vest4		0.10
MutPred		0.26		Loss of stability (P = 0.0296)
MVP		0.076
MPC		0.0036
ClinPred		0.14	T
GERP RS		2.4
Varity_R		0.094
gMVP		0.020
Mutation Taster		=99/1	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: rs751427720; hg19: chrX-133379778;