22-30371650-A-G

Position:

• chr22-30371650-A-G

Variant summary

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

The NM_001017437.5(CCDC157):​c.1046A>G​(p.Glu349Gly) variant causes a missense, splice region 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. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC157 NM_001017437.5 missense, splice_region
• Scores: Splicing: ADA: 0.001116
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.466

Genes affected

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

KIAA1656 (HGNC:):

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]

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=0.12838298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC157	NM_001017437.5	c.1046A>G	p.Glu349Gly	missense_variant, splice_region_variant	6/12	ENST00000338306.8	NP_001017437.3
KIAA1656	NR_046312.1	n.4766T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8	c.1046A>G	p.Glu349Gly	missense_variant, splice_region_variant	6/12	5	NM_001017437.5	ENSP00000343087	P1
CCDC157	ENST00000405659.5	c.1046A>G	p.Glu349Gly	missense_variant, splice_region_variant	6/12	1		ENSP00000385357	P1
CCDC157	ENST00000475975.5	n.1670A>G		non_coding_transcript_exon_variant	4/10	2
RNF215	ENST00000332468.5	c.*5125T>C		3_prime_UTR_variant, NMD_transcript_variant	3/3	5		ENSP00000487588

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Apr 15, 2024

The c.1046A>G (p.E349G) alteration is located in exon 6 (coding exon 4) of the CCDC157 gene. This alteration results from a A to G substitution at nucleotide position 1046, causing the glutamic acid (E) at amino acid position 349 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.62	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.21
Sift	Benign	0.10	T;T
Sift4G	Benign	0.096	T;T
Polyphen		0.19	B;B
Vest4		0.40
MutPred		0.096		Loss of stability (P = 0.0229);Loss of stability (P = 0.0229);
MVP		0.29
MPC		0.50
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.15
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0011
dbscSNV1_RF	Benign	0.018
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: chr22-30767639;