chr22-30366151-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001017437.5(CCDC157):​c.151G>T​(p.Asp51Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.17
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC157	NM_001017437.5	c.151G>T	p.Asp51Tyr	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>T	p.Asp51Tyr	missense_variant	Exon 3 of 12	5	NM_001017437.5	ENSP00000343087.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
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	0.91	D;.;T;D;D
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.85	D;D;D;D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.2	.;M;M;.;.
PhyloP100		9.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.6	D;D;D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0040	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D
Polyphen		1.0	.;D;D;.;.
Vest4		0.91
MutPred		0.53		Gain of phosphorylation at D51 (P = 0.0351);Gain of phosphorylation at D51 (P = 0.0351);Gain of phosphorylation at D51 (P = 0.0351);Gain of phosphorylation at D51 (P = 0.0351);Gain of phosphorylation at D51 (P = 0.0351);
MVP		0.63
MPC		0.51
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.55
gMVP		0.72
Mutation Taster		=51/49	polymorphism

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: rs740223; hg19: chr22-30762140;