16-1434514-G-C

Variant names:

• chr16-1434514-G-C
• rs1358130787
• NM_001143980.3:c.1898C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001143980.3(CCDC154):​c.1898C>G​(p.Ser633Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,395,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CCDC154 NM_001143980.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0860
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15229559).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143980.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC154	NM_001143980.3	MANE Select	c.1898C>G	p.Ser633Cys	missense	Exon 17 of 17	NP_001137452.1	A6NI56
	PERCC1	NM_001365310.2	MANE Select	c.*1117G>C		downstream_gene	N/A	NP_001352239.1	A0A1W2PR82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC154	ENST00000389176.4	TSL:5 MANE Select	c.1898C>G	p.Ser633Cys	missense	Exon 17 of 17	ENSP00000373828.4	A6NI56
	CCDC154	ENST00000409671.5	TSL:1	c.1463C>G	p.Ser488Cys	missense	Exon 16 of 16	ENSP00000386744.1	B7ZBA8
	CCDC154	ENST00000463299.2	TSL:1	n.343C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000652 AC: 1 AN: 153452 AF XY: 0.0000123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000169

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1395878 Hom.: 0 Cov.: 50 AF XY: 0.00000145 AC XY: 1 AN XY: 688286

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 35644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25132

East Asian (EAS) AF: 0.00 AC: 0 AN: 35710

South Asian (SAS) AF: 0.00 AC: 0 AN: 79158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078266

Other (OTH) AF: 0.00 AC: 0 AN: 57882

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.92
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.086
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.020
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.88	P
Vest4		0.15
MutPred		0.37		Gain of catalytic residue at L641 (P = 0.0237)
MVP		0.014
MPC		0.00025
ClinPred		0.090	T
GERP RS		-0.87
Varity_R		0.048
gMVP		0.038

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: rs1358130787; hg19: chr16-1484515;