rs12167903

Positions:

• chr22-30370477-C-A
• chr22-30370477-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.572C>A​(p.Pro191His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P191L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=0.15695205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC157	NM_001017437.5	c.572C>A	p.Pro191His	missense_variant	5/12	ENST00000338306.8	NP_001017437.3
KIAA1656	NR_046312.1	n.5939G>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8	c.572C>A	p.Pro191His	missense_variant	5/12	5	NM_001017437.5	ENSP00000343087	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0062	T;T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.036
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.40	.;T;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.7	M;M;.;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N;N;D;D
REVEL	Benign	0.059
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.33
MutPred		0.31		Loss of disorder (P = 0.0573);Loss of disorder (P = 0.0573);Loss of disorder (P = 0.0573);Loss of disorder (P = 0.0573);
MVP		0.26
MPC		0.50
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.089
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs12167903; hg19: chr22-30766466;