chr19-41316773-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_052848.3(CCDC97):c.436C>T(p.Arg146Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,609,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000083 ( 0 hom. )
Consequence
CCDC97
NM_052848.3 missense
NM_052848.3 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 1.47
Genes affected
CCDC97 (HGNC:28289): (coiled-coil domain containing 97)
TGFB1 (HGNC:11766): (transforming growth factor beta 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGFB family members. This encoded protein regulates cell proliferation, differentiation and growth, and can modulate expression and activation of other growth factors including interferon gamma and tumor necrosis factor alpha. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.021475017).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CCDC97 | NM_052848.3 | c.436C>T | p.Arg146Trp | missense_variant | 2/5 | ENST00000269967.4 | |
CCDC97 | NM_001346100.2 | c.241C>T | p.Arg81Trp | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CCDC97 | ENST00000269967.4 | c.436C>T | p.Arg146Trp | missense_variant | 2/5 | 1 | NM_052848.3 | P1 | |
TGFB1 | ENST00000598758.5 | n.303-14053G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000552 AC: 84AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000153 AC: 37AN: 242166Hom.: 0 AF XY: 0.000159 AC XY: 21AN XY: 131848
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GnomAD4 exome AF: 0.0000831 AC: 121AN: 1456674Hom.: 0 Cov.: 33 AF XY: 0.0000843 AC XY: 61AN XY: 723636
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GnomAD4 genome AF: 0.000551 AC: 84AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74484
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 17, 2023 | The c.436C>T (p.R146W) alteration is located in exon 2 (coding exon 2) of the CCDC97 gene. This alteration results from a C to T substitution at nucleotide position 436, causing the arginine (R) at amino acid position 146 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at