19-41319615-CCC-AGT

Variant names:

• chr19-41319615-CCC-AGT
• NM_052848.3:c.544_546delCCCinsAGT
• CCDC97 p.Pro182Ser

Variant summary

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

The NM_052848.3(CCDC97):​c.544_546delCCCinsAGT​(p.Pro182Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC97 NM_052848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64
• Publications: 0 publications found

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]

TGFB1 Gene-Disease associations (from GenCC):

• Camurati-Engelmann disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• inflammatory bowel disease, immunodeficiency, and encephalopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052848.3. 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
	CCDC97	NM_052848.3	MANE Select	c.544_546delCCCinsAGT	p.Pro182Ser	missense	N/A	NP_443080.1	Q96F63
	CCDC97	NM_001346100.2		c.349_351delCCCinsAGT	p.Pro117Ser	missense	N/A	NP_001333029.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC97	ENST00000269967.4	TSL:1 MANE Select	c.544_546delCCCinsAGT	p.Pro182Ser	missense	N/A	ENSP00000269967.2	Q96F63
	CCDC97	ENST00000886246.1		c.637_639delCCCinsAGT	p.Pro213Ser	missense	N/A	ENSP00000556305.1
	TGFB1	ENST00000598758.5	TSL:5	n.302+12511_302+12513delGGGinsACT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-41825520;