Genetic Variant CCDC160:p.Thr194Met (chrX-134245381-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001353453.3(CCDC160):c.581C>T(p.Thr194Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,188,680 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000012 ( 0 hom. 3 hem. )

Consequence

CCDC160
NM_001353453.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.63

Publications

2 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037948728).

BS2

High Hemizygotes in GnomAdExome4 at 3 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.581C>T	p.Thr194Met	missense	Exon 3 of 3	NP_001340382.1	A6NGH7
CCDC160	NM_001101357.3		c.581C>T	p.Thr194Met	missense	Exon 2 of 2	NP_001094827.1	A6NGH7
CCDC160	NM_001393996.1		c.581C>T	p.Thr194Met	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.581C>T	p.Thr194Met	missense	Exon 3 of 3	ENSP00000511932.1	A6NGH7
CCDC160	ENST00000370809.5	TSL:5	c.581C>T	p.Thr194Met	missense	Exon 2 of 2	ENSP00000359845.4	A6NGH7
CCDC160	ENST00000517294.5	TSL:5	c.581C>T	p.Thr194Met	missense	Exon 3 of 3	ENSP00000427951.1	A6NGH7

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

111826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000276

AC:

AN:

144765

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000974

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000896

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000159

Gnomad OTH exome

AF:

0.000268

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1076854

Hom.:

Cov.:

AF XY:

0.00000861

AC XY:

AN XY:

348606

show subpopulations

African (AFR)

AF:

0.0000778

AC:

AN:

25704

American (AMR)

AF:

0.0000318

AC:

AN:

31438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18787

East Asian (EAS)

AF:

0.0000671

AC:

AN:

29822

South Asian (SAS)

AF:

0.00

AC:

AN:

49377

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39755

Middle Eastern (MID)

AF:

0.000245

AC:

AN:

4079

European-Non Finnish (NFE)

AF:

0.00000721

AC:

AN:

832552

Other (OTH)

AF:

0.0000221

AC:

AN:

45340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

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:

0.0000268

AC:

AN:

111826

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34056

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30856

American (AMR)

AF:

0.00

AC:

AN:

10536

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2637

East Asian (EAS)

AF:

0.00

AC:

AN:

3606

South Asian (SAS)

AF:

0.00

AC:

AN:

2724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5929

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53112

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000323

Hom.:

Bravo

AF:

0.0000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0010

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.077

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.40

M_CAP

Benign

0.037

MetaRNN

Benign

0.038

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.050

PhyloP100

-3.6

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.33

REVEL

Benign

0.22

Sift

Benign

0.16

Sift4G

Benign

0.14

Polyphen

0.11

Vest4

0.10

MutPred

0.14

Loss of phosphorylation at T194 (P = 0.0418)

MVP

0.092

MPC

0.0023

ClinPred

0.015

GERP RS

-10

Varity_R

0.017

gMVP

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over