Variant 22-30369496-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001017437.5(CCDC157):c.313C>T(p.Pro105Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000277 in 1,444,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CCDC157
NM_001017437.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

CCDC157 (HGNC:33854): (coiled-coil domain containing 157)

CCDC157 links:

RNF215 (HGNC:33434): (ring finger protein 215) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in Golgi to vacuole transport; protein targeting to vacuole; and ubiquitin-dependent protein catabolic process. Predicted to be integral component of membrane. Predicted to be part of Golgi transport complex. Predicted to be active in endosome; membrane; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RNF215 links:

CCDC157 (HGNC:):

CCDC157 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=0.2312913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC157	NM_001017437.5 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	4/12	ENST00000338306.8	NP_001017437.3	Q569K6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8 linkuse as main transcript	c.313C>T	p.Pro105Ser	missense_variant	4/12	5	NM_001017437.5	ENSP00000343087.3		Q569K6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1444662

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

718090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.0000168

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.313C>T (p.P105S) alteration is located in exon 4 (coding exon 2) of the CCDC157 gene. This alteration results from a C to T substitution at nucleotide position 313, causing the proline (P) at amino acid position 105 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

T;T;T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.69

.;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;L;.;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.5

N;N;D;D

REVEL

Benign

0.14

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

1.0

D;D;.;.

Vest4

0.56

MutPred

0.29

Loss of catalytic residue at P105 (P = 0.0025);Loss of catalytic residue at P105 (P = 0.0025);Loss of catalytic residue at P105 (P = 0.0025);Loss of catalytic residue at P105 (P = 0.0025);

MVP

0.29

MPC

0.47

ClinPred

0.89

GERP RS

5.3

Varity_R

0.082

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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