5-42759144-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134848.2(CCDC152):c.23G>A(p.Cys8Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CCDC152 NM_001134848.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0620

Genes affected

CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05953732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC152	NM_001134848.2	c.23G>A	p.Cys8Tyr	missense_variant	2/9	ENST00000361970.10
CCDC152	XM_047416584.1	c.86G>A	p.Cys29Tyr	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC152	ENST00000361970.10	c.23G>A	p.Cys8Tyr	missense_variant	2/9	1	NM_001134848.2	P1
CCDC152	ENST00000388827.4	c.23G>A	p.Cys8Tyr	missense_variant	2/7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398502 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 689780

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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

Jun 17, 2022

The c.23G>A (p.C8Y) alteration is located in exon 2 (coding exon 1) of the CCDC152 gene. This alteration results from a G to A substitution at nucleotide position 23, causing the cysteine (C) at amino acid position 8 to be replaced by a tyrosine (Y). 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	0.070
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	11
Dann	Benign	0.69
DEOGEN2	Benign	0.10	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.060	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.045
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.0010	B;.
Vest4		0.16
MutPred		0.16		Loss of methylation at K11 (P = 0.0496);Loss of methylation at K11 (P = 0.0496);
MVP		0.040
ClinPred		0.068	T
GERP RS		-1.1
Varity_R		0.26
gMVP		0.073

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: rs1486844819; hg19: chr5-42759246;