chr16-1434482-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001143980.3(CCDC154):​c.1930G>C​(p.Gly644Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,549,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

CCDC154
NM_001143980.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.82
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038635075).
BP6
Variant 16-1434482-C-G is Benign according to our data. Variant chr16-1434482-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3828265.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC154NM_001143980.3 linkc.1930G>C p.Gly644Arg missense_variant Exon 17 of 17 ENST00000389176.4 NP_001137452.1 A6NI56
PERCC1NM_001365310.2 linkc.*1085C>G downstream_gene_variant ENST00000640283.2 NP_001352239.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC154ENST00000389176.4 linkc.1930G>C p.Gly644Arg missense_variant Exon 17 of 17 5 NM_001143980.3 ENSP00000373828.4 A6NI56A0A590PWR5
PERCC1ENST00000640283.2 linkc.*1085C>G downstream_gene_variant 5 NM_001365310.2 ENSP00000492108.2 A0A1W2PR82

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152176
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000358
AC:
5
AN:
1397702
Hom.:
0
Cov.:
51
AF XY:
0.00000145
AC XY:
1
AN XY:
689346
show subpopulations
Gnomad4 AFR exome
AF:
0.000127
Gnomad4 AMR exome
AF:
0.0000280
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152294
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000168
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000416

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 21, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.11
DANN
Benign
0.22
DEOGEN2
Benign
0.0015
T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
1.0
N;N
REVEL
Benign
0.075
Sift
Benign
0.29
T;T
Sift4G
Benign
0.078
T;T
Polyphen
0.0040
B;.
Vest4
0.066
MutPred
0.32
Gain of MoRF binding (P = 0.0285);.;
MVP
0.014
MPC
0.00025
ClinPred
0.052
T
GERP RS
2.3
Varity_R
0.034
gMVP
0.039

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs576528390; hg19: chr16-1484483; API