22-30370780-C-T

Position:

• chr22-30370780-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001017437.5(CCDC157):​c.875C>T​(p.Ala292Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70

Genes affected

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

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]

CCDC157 (HGNC:):

ACMG classification

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=0.17226043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC157	NM_001017437.5	c.875C>T	p.Ala292Val	missense_variant	5/12	ENST00000338306.8	NP_001017437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8	c.875C>T	p.Ala292Val	missense_variant	5/12	5	NM_001017437.5	ENSP00000343087.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.875C>T (p.A292V) alteration is located in exon 5 (coding exon 3) of the CCDC157 gene. This alteration results from a C to T substitution at nucleotide position 875, causing the alanine (A) at amino acid position 292 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.55	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.054
Sift	Benign	0.31	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.86	P;P
Vest4		0.29
MutPred		0.12		Loss of ubiquitination at K288 (P = 0.0777);Loss of ubiquitination at K288 (P = 0.0777);
MVP		0.20
MPC		0.22
ClinPred		0.72	D
GERP RS		4.4
Varity_R		0.087
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-30766769; COSMIC: COSV57842387; COSMIC: COSV57842387;