Genetic Variant CCDC142:p.Ser742Cys (chr2-74474574-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365575.2(CCDC142):c.2225C>G(p.Ser742Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC142
NM_001365575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.707

Variant links:

Genes affected

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

CCDC142 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23120803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC142	NM_001365575.2 link	c.2225C>G	p.Ser742Cys	missense_variant	Exon 9 of 9	ENST00000393965.8	NP_001352504.1
CCDC142	NM_032779.4 link	c.2204C>G	p.Ser735Cys	missense_variant	Exon 9 of 9		NP_116168.3	Q17RM4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC142	ENST00000393965.8 link	c.2225C>G	p.Ser742Cys	missense_variant	Exon 9 of 9	1	NM_001365575.2	ENSP00000377537.3	Q17RM4-1
CCDC142	ENST00000290418.4 link	c.2204C>G	p.Ser735Cys	missense_variant	Exon 9 of 9	2		ENSP00000290418.4	Q17RM4-2
CCDC142	ENST00000473278.1 link	n.795C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
CCDC142	ENST00000454193.5 link	n.1699+342C>G		intron_variant	Intron 8 of 10	2		ENSP00000415532.1	H7C450

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1459364

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726046

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2204C>G (p.S735C) alteration is located in exon 9 (coding exon 9) of the CCDC142 gene. This alteration results from a C to G substitution at nucleotide position 2204, causing the serine (S) at amino acid position 735 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

T;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.45

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.017

D;D

Sift4G

Benign

0.081

T;T

Polyphen

0.99

D;D

Vest4

0.31

MutPred

0.33

Loss of glycosylation at S742 (P = 0.0133);.;

MVP

0.65

MPC

0.74

ClinPred

0.69

GERP RS

1.9

Varity_R

0.050

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over