22-30366151-G-C

Variant names:

• chr22-30366151-G-C
• rs740223
• NM_001017437.5:c.151G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001017437.5(CCDC157):​c.151G>C​(p.Asp51His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D51N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.17

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC157	NM_001017437.5	c.151G>C	p.Asp51His	missense_variant	Exon 3 of 12	ENST00000338306.8	NP_001017437.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC157	ENST00000338306.8	c.151G>C	p.Asp51His	missense_variant	Exon 3 of 12	5	NM_001017437.5	ENSP00000343087.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250802 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135640

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461418 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74324

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T;T;T;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;.;T;D;D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	.;M;M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.7	D;D;D;D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0080	D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.89
MutPred		0.56		Loss of stability (P = 0.0949);Loss of stability (P = 0.0949);Loss of stability (P = 0.0949);Loss of stability (P = 0.0949);Loss of stability (P = 0.0949);
MVP		0.44
MPC		0.50
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs740223; hg19: chr22-30762140;