Genetic Variant CCDC160:p.Thr36Met (chrX-134244907-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001353453.3(CCDC160):c.107C>T(p.Thr36Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000599 in 1,202,818 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000061 ( 0 hom. 21 hem. )

Consequence

CCDC160
NM_001353453.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.274

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02270183).

BP6

Variant X-134244907-C-T is Benign according to our data. Variant chrX-134244907-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2592063.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC160	NM_001353453.3 link	c.107C>T	p.Thr36Met	missense_variant	Exon 3 of 3	ENST00000695460.1	NP_001340382.1
CCDC160	NM_001101357.3 link	c.107C>T	p.Thr36Met	missense_variant	Exon 2 of 2		NP_001094827.1	A6NGH7
CCDC160	NM_001393996.1 link	c.107C>T	p.Thr36Met	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.107C>T	p.Thr36Met	missense_variant	Exon 3 of 3		NM_001353453.3	ENSP00000511932.1	A6NGH7
CCDC160	ENST00000370809.5 link	c.107C>T	p.Thr36Met	missense_variant	Exon 2 of 2	5		ENSP00000359845.4	A6NGH7
CCDC160	ENST00000517294.5 link	c.107C>T	p.Thr36Met	missense_variant	Exon 3 of 3	5		ENSP00000427951.1	A6NGH7

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111579

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33831

show subpopulations

Gnomad AFR

AF:

0.0000652

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000301

AC:

AN:

165894

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

54148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000123

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000412

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000614

AC:

AN:

1091239

Hom.:

Cov.:

AF XY:

0.0000587

AC XY:

AN XY:

357753

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000382

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000775

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000448

AC:

AN:

111579

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33831

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 12, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.075

DANN

Benign

0.11

DEOGEN2

Benign

0.057

T;T

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.42

T;.

M_CAP

Benign

0.0042

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.49

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.88

N;N

REVEL

Benign

0.032

Sift

Benign

0.39

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.029

B;B

Vest4

0.048

MVP

0.014

MPC

0.0056

ClinPred

0.028

GERP RS

-7.5

Varity_R

0.016

gMVP

0.026

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