Genetic Variant NM_001353453.3:c.20A>T (chrX-134244820-A-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H7R) has been classified 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

Publications

0 publications found

Variant links:

Genes affected

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

CCDC160 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAdExome4 at 7 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC160	NM_001353453.3	MANE Select	c.20A>T	p.His7Leu	missense	Exon 3 of 3	NP_001340382.1	A6NGH7
CCDC160	NM_001101357.3		c.20A>T	p.His7Leu	missense	Exon 2 of 2	NP_001094827.1	A6NGH7
CCDC160	NM_001393996.1		c.20A>T	p.His7Leu	missense	Exon 3 of 3	NP_001380925.1	A6NGH7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC160	ENST00000695460.1	MANE Select	c.20A>T	p.His7Leu	missense	Exon 3 of 3	ENSP00000511932.1	A6NGH7
CCDC160	ENST00000370809.5	TSL:5	c.20A>T	p.His7Leu	missense	Exon 2 of 2	ENSP00000359845.4	A6NGH7
CCDC160	ENST00000517294.5	TSL:5	c.20A>T	p.His7Leu	missense	Exon 3 of 3	ENSP00000427951.1	A6NGH7

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112208

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000152

AC:

AN:

131566

AF XY:

0.0000285

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 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

African (AFR)

AF:

0.00

AC:

AN:

24597

American (AMR)

AF:

0.0000387

AC:

AN:

25834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17697

East Asian (EAS)

AF:

0.00

AC:

AN:

29641

South Asian (SAS)

AF:

0.00

AC:

AN:

46826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3985

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

824479

Other (OTH)

AF:

0.00

AC:

AN:

44366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34358

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30893

American (AMR)

AF:

0.0000951

AC:

AN:

10510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3598

South Asian (SAS)

AF:

0.00

AC:

AN:

2713

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6155

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53256

Other (OTH)

AF:

0.00

AC:

AN:

1513

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000167

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.61

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.39

M_CAP

Benign

0.016

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.3

PhyloP100

2.5

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.17

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.43

MutPred

0.28

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

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over