22-30370477-C-T

Variant names:

• chr22-30370477-C-T
• rs12167903
• NM_001017437.5:c.572C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017437.5(CCDC157):​c.572C>T​(p.Pro191Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00413 in 1,614,110 control chromosomes in the GnomAD database, including 224 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.021 (109 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (115 hom.)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 7 publications found

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]

KIAA1656 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002074033).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017437.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC157	NM_001017437.5	MANE Select	c.572C>T	p.Pro191Leu	missense	Exon 5 of 12	NP_001017437.3
	CCDC157	NM_001318334.2		c.572C>T	p.Pro191Leu	missense	Exon 5 of 12	NP_001305263.2
	KIAA1656	NR_046312.1		n.5939G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC157	ENST00000338306.8	TSL:5 MANE Select	c.572C>T	p.Pro191Leu	missense	Exon 5 of 12	ENSP00000343087.3
	CCDC157	ENST00000405659.5	TSL:1	c.572C>T	p.Pro191Leu	missense	Exon 5 of 12	ENSP00000385357.1
	CCDC157	ENST00000430839.5	TSL:3	c.572C>T	p.Pro191Leu	missense	Exon 5 of 5	ENSP00000401837.1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3242 AN: 152220 Hom.: 110 Cov.: 33

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00575 AC: 1445 AN: 251454 AF XY: 0.00441

Gnomad AFR exome AF: 0.0746

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000431

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00235 AC: 3431 AN: 1461772 Hom.: 115 Cov.: 31 AF XY: 0.00211 AC XY: 1534 AN XY: 727192

African (AFR) AF: 0.0789 AC: 2643 AN: 33480

American (AMR) AF: 0.00494 AC: 221 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5768

European-Non Finnish (NFE) AF: 0.000147 AC: 163 AN: 1112012

Other (OTH) AF: 0.00586 AC: 354 AN: 60394

GnomAD4 genome AF: 0.0213 AC: 3243 AN: 152338 Hom.: 109 Cov.: 33 AF XY: 0.0207 AC XY: 1541 AN XY: 74490

African (AFR) AF: 0.0722 AC: 3003 AN: 41564

American (AMR) AF: 0.0116 AC: 177 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68032

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.00931 Hom.: 94

Bravo AF: 0.0252

ESP6500AA AF: 0.0672 AC: 296

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00684 AC: 830

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000830

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.051
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.020	D
Polyphen		0.18	B
Vest4		0.20
MVP		0.22
MPC		0.47
ClinPred		0.033	T
GERP RS		4.3
Varity_R		0.057
gMVP		0.42
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12167903; hg19: chr22-30766466; COSMIC: COSV57838894; COSMIC: COSV57838894;