rs561677923

Variant summary

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

The NM_001143980.3(CCDC154):​c.1474G>T​(p.Glu492*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,396,256 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. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

CCDC154
NM_001143980.3 stop_gained

Scores

2
3
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.49
Variant links:
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]

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ACMG classification

Classification made for transcript

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
CCDC154NM_001143980.3 linkc.1474G>T p.Glu492* stop_gained Exon 13 of 17 ENST00000389176.4 NP_001137452.1 A6NI56

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC154ENST00000389176.4 linkc.1474G>T p.Glu492* stop_gained Exon 13 of 17 5 NM_001143980.3 ENSP00000373828.4 A6NI56A0A590PWR5
CCDC154ENST00000409671.5 linkc.1039G>T p.Glu347* stop_gained Exon 12 of 16 1 ENSP00000386744.1 B7ZBA8
CCDC154ENST00000483702.5 linkn.271G>T non_coding_transcript_exon_variant Exon 3 of 6 3 ENSP00000456484.1 H3BS06

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.00000647
AC:
1
AN:
154512
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
82120
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000166
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000501
AC:
7
AN:
1396256
Hom.:
0
Cov.:
33
AF XY:
0.00000290
AC XY:
2
AN XY:
688712
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000560
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:
0.00000463
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000434
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.53
D
BayesDel_noAF
Pathogenic
0.53
CADD
Pathogenic
46
DANN
Uncertain
0.99
Eigen
Uncertain
0.52
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.16
N
Vest4
0.068
GERP RS
4.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs561677923; hg19: chr16-1486459; API