22-30370737-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001017437.5(CCDC157):c.832G>A(p.Glu278Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,450 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCDC157
NM_001017437.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.18

Variant links:

Genes affected

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

CCDC157 links:

KIAA1656 (HGNC:):

KIAA1656 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27151698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC157	NM_001017437.5 linkuse as main transcript	c.832G>A	p.Glu278Lys	missense_variant	5/12	ENST00000338306.8
KIAA1656	NR_046312.1 linkuse as main transcript	n.5679C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC157	ENST00000338306.8 linkuse as main transcript	c.832G>A	p.Glu278Lys	missense_variant	5/12	5	NM_001017437.5	P1
CCDC157	ENST00000405659.5 linkuse as main transcript	c.832G>A	p.Glu278Lys	missense_variant	5/12	1		P1
CCDC157	ENST00000475975.5 linkuse as main transcript	n.757G>A		non_coding_transcript_exon_variant	4/10	2
RNF215	ENST00000332468.5 linkuse as main transcript	c.*6038C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249328

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135172

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461196

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726914

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

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

Jul 11, 2023

The c.832G>A (p.E278K) alteration is located in exon 5 (coding exon 3) of the CCDC157 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the glutamic acid (E) at amino acid position 278 to be replaced by a lysine (K). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.020

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.14

Sift

Benign

0.062

T;T

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.74

P;P

Vest4

0.39

MutPred

0.39

Gain of methylation at E278 (P = 0.0172);Gain of methylation at E278 (P = 0.0172);

MVP

0.23

MPC

0.10

ClinPred

0.83

GERP RS

4.4

Varity_R

0.30

gMVP

0.59

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