rs750721196

Variant names:

• chr16-1434452-C-A
• NM_001143980.3:c.1960G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1434452-C-A
• chr16-1434452-C-G

Variant summary

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

The NM_001143980.3(CCDC154):​c.1960G>T​(p.Glu654*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,034 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.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CCDC154 NM_001143980.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.850

Genes affected

CCDC154 (HGNC:34454): (coiled-coil domain containing 154) Predicted to be involved in bone mineralization involved in bone maturation. Predicted to act upstream of or within bone resorption; odontogenesis of dentin-containing tooth; and tooth eruption. Predicted to be located in early endosome. [provided by Alliance of Genome Resources, Apr 2022]

PERCC1 (HGNC:52293): (proline and glutamate rich with coiled coil 1) Predicted to be involved in digestive tract morphogenesis and enteroendocrine cell differentiation. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC154	NM_001143980.3	c.1960G>T	p.Glu654*	stop_gained	Exon 17 of 17	ENST00000389176.4	NP_001137452.1
PERCC1	NM_001365310.2	c.*1055C>A		downstream_gene_variant		ENST00000640283.2	NP_001352239.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC154	ENST00000389176.4	c.1960G>T	p.Glu654*	stop_gained	Exon 17 of 17	5	NM_001143980.3	ENSP00000373828.4
PERCC1	ENST00000640283.2	c.*1055C>A		downstream_gene_variant		5	NM_001365310.2	ENSP00000492108.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398034 Hom.: 0 Cov.: 60 AF XY: 0.00000145 AC XY: 1 AN XY: 689516

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.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	37
DANN	Uncertain	0.98
Eigen	Benign	0.065
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.18	N
Vest4		0.041
GERP RS		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
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: chr16-1484453;