Genetic Variant CCDC160:p.His7Leu (chrX-134244820-A-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001353453.3(CCDC160):c.20A>T(p.His7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,168,995 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 7 hem. )

Consequence

CCDC160
NM_001353453.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47

Variant links:

Genes affected

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

CCDC160 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3073234).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC160	NM_001353453.3 link	c.20A>T	p.His7Leu	missense_variant	Exon 3 of 3	ENST00000695460.1	NP_001340382.1
CCDC160	NM_001101357.3 link	c.20A>T	p.His7Leu	missense_variant	Exon 2 of 2		NP_001094827.1	A6NGH7
CCDC160	NM_001393996.1 link	c.20A>T	p.His7Leu	missense_variant	Exon 3 of 3		NP_001380925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC160	ENST00000695460.1 link	c.20A>T	p.His7Leu	missense_variant	Exon 3 of 3		NM_001353453.3	ENSP00000511932.1	A6NGH7
CCDC160	ENST00000370809.5 link	c.20A>T	p.His7Leu	missense_variant	Exon 2 of 2	5		ENSP00000359845.4	A6NGH7
CCDC160	ENST00000517294.5 link	c.20A>T	p.His7Leu	missense_variant	Exon 3 of 3	5		ENSP00000427951.1	A6NGH7

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34358

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000951

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

GnomAD3 exomes

AF:

0.0000152

AC:

AN:

131566

Hom.:

AF XY:

0.0000285

AC XY:

AN XY:

35084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1056787

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

338495

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000387

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000951

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jul 11, 2017

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Uncertain

0.61

D;D

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.39

T;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.98

D;D

Vest4

0.43

MutPred

0.28

Gain of helix (P = 0.062);Gain of helix (P = 0.062);

MVP

0.11

MPC

0.0027

ClinPred

0.41

GERP RS

5.0

Varity_R

0.63

gMVP

0.11

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over