chr5-42783575-A-T

Variant names:

• chr5-42783575-A-T
• NM_001134848.2:c.429A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134848.2(CCDC152):​c.429A>T​(p.Lys143Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000838 in 1,193,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: CCDC152 NM_001134848.2 missense, splice_region
• Scores: Splicing: ADA: 0.9256
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.37

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21174407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC152	NM_001134848.2	c.429A>T	p.Lys143Asn	missense_variant, splice_region_variant	Exon 6 of 9	ENST00000361970.10	NP_001128320.1
CCDC152	XM_047416584.1	c.492A>T	p.Lys164Asn	missense_variant, splice_region_variant	Exon 6 of 9		XP_047272540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC152	ENST00000361970.10	c.429A>T	p.Lys143Asn	missense_variant, splice_region_variant	Exon 6 of 9	1	NM_001134848.2	ENSP00000354888.5
CCDC152	ENST00000388827.4	c.263-13254A>T		intron_variant	Intron 4 of 6	2		ENSP00000373479.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.38e-7 AC: 1 AN: 1193396 Hom.: 0 Cov.: 20 AF XY: 0.00000171 AC XY: 1 AN XY: 584626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000359

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.061
Sift	Benign	0.047	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.93	P
Vest4		0.25
MutPred		0.20		Loss of methylation at K143 (P = 0.0013);
MVP		0.12
ClinPred		0.95	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Benign	0.60
SpliceAI score (max)		0.020		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: chr5-42783677;