22-30372180-A-C

Position:

• chr22-30372180-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001017437.5(CCDC157):​c.1229A>C​(p.Gln410Pro) 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: 33)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39721528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC157	NM_001017437.5	c.1229A>C	p.Gln410Pro	missense_variant	7/12	ENST00000338306.8	NP_001017437.3
KIAA1656	NR_046312.1	n.4236T>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8	c.1229A>C	p.Gln410Pro	missense_variant	7/12	5	NM_001017437.5	ENSP00000343087	P1
CCDC157	ENST00000405659.5	c.1229A>C	p.Gln410Pro	missense_variant	7/12	1		ENSP00000385357	P1
CCDC157	ENST00000475975.5	n.1853A>C		non_coding_transcript_exon_variant	5/10	2
RNF215	ENST00000332468.5	c.*4595T>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	5		ENSP00000487588

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

Mar 29, 2022

The c.1229A>C (p.Q410P) alteration is located in exon 7 (coding exon 5) of the CCDC157 gene. This alteration results from a A to C substitution at nucleotide position 1229, causing the glutamine (Q) at amino acid position 410 to be replaced by a proline (P). 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	0.37
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.46	.;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.93	N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.19
Sift	Benign	0.23	T;T
Sift4G	Uncertain	0.021	D;D
Polyphen		0.96	D;D
Vest4		0.56
MutPred		0.18		Loss of MoRF binding (P = 0.0653);Loss of MoRF binding (P = 0.0653);
MVP		0.19
MPC		0.50
ClinPred		0.82	D
GERP RS		4.1
Varity_R		0.28
gMVP		0.56

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: chr22-30768169;