22-30366145-G-A

Variant summary

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

The NM_001017437.5(CCDC157):c.145G>A(p.Asp49Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC157 NM_001017437.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

Genes affected

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

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=0.280624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC157	NM_001017437.5	c.145G>A	p.Asp49Asn	missense_variant	3/12	ENST00000338306.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC157	ENST00000338306.8	c.145G>A	p.Asp49Asn	missense_variant	3/12	5	NM_001017437.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Sep 06, 2022

The c.145G>A (p.D49N) alteration is located in exon 3 (coding exon 1) of the CCDC157 gene. This alteration results from a G to A substitution at nucleotide position 145, causing the aspartic acid (D) at amino acid position 49 to be replaced by an asparagine (N). 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	Benign	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T;T;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T;.;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	0.69	N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D;N;N;D;D
REVEL	Benign	0.10
Sift	Benign	0.14	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;D;D
Polyphen		0.86	.;P;P;.;.
Vest4		0.12
MutPred		0.33		Gain of catalytic residue at D49 (P = 0.0199);Gain of catalytic residue at D49 (P = 0.0199);Gain of catalytic residue at D49 (P = 0.0199);Gain of catalytic residue at D49 (P = 0.0199);Gain of catalytic residue at D49 (P = 0.0199);
MVP		0.43
MPC		0.46
ClinPred		0.94	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.31

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: chr22-30762134;