Genetic Variant CCDC142:p.Ser683Arg (chr2-74474752-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001365575.2(CCDC142):c.2047A>C(p.Ser683Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,450 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S683I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCDC142
NM_001365575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Publications

0 publications found

Variant links:

Genes affected

CCDC142 (HGNC:25889): (coiled-coil domain containing 142)

CCDC142 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32933277).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365575.2. 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
	CCDC142	NM_001365575.2	MANE Select	c.2047A>C	p.Ser683Arg	missense	Exon 9 of 9	NP_001352504.1	Q17RM4-1
	CCDC142	NM_032779.4		c.2026A>C	p.Ser676Arg	missense	Exon 9 of 9	NP_116168.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC142	ENST00000393965.8	TSL:1 MANE Select	c.2047A>C	p.Ser683Arg	missense	Exon 9 of 9	ENSP00000377537.3	Q17RM4-1
CCDC142	ENST00000904898.1		c.2089A>C	p.Ser697Arg	missense	Exon 9 of 9	ENSP00000574957.1
CCDC142	ENST00000969128.1		c.2068A>C	p.Ser690Arg	missense	Exon 9 of 9	ENSP00000639187.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250964

AF XY:

0.00000737

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461450

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111716

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.72

M_CAP

Benign

0.039

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.0

PhyloP100

3.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

REVEL

Benign

0.10

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0090

Polyphen

0.95

Vest4

0.42

MutPred

0.17

Loss of phosphorylation at S683 (P = 0.0452)

MVP

0.77

MPC

0.50

ClinPred

0.81

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.38

Mutation Taster

=83/17

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