1-156346818-AAC-TCG

Variant names:

• chr1-156346818-AAC-TCG
• NM_001304817.2:c.214_216delAACinsTCG
• TSACC p.Asn72Ser

Variant summary

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

The NM_001304817.2(TSACC):​c.214_216delAACinsTCG​(p.Asn72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 31)
• Consequence: TSACC NM_001304817.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70
• Publications: 0 publications found

Genes affected

TSACC (HGNC:30636): (TSSK6 activating cochaperone) Enables chaperone binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCT3 (HGNC:1616): (chaperonin containing TCP1 subunit 3) The protein encoded by this gene is a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC). This complex consists of two identical stacked rings, each containing eight different proteins. Unfolded polypeptides enter the central cavity of the complex and are folded in an ATP-dependent manner. The complex folds various proteins, including actin and tubulin. Alternate transcriptional splice variants have been characterized for this gene. In addition, a pseudogene of this gene has been found on chromosome 8. [provided by RefSeq, Aug 2010]

CCT3 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• neurodevelopmental disorder with speech or visual impairment and brain hypomyelination

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304817.2. 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
	TSACC	NM_001304817.2	MANE Select	c.214_216delAACinsTCG	p.Asn72Ser	missense	N/A	NP_001291746.1	Q96A04
	TSACC	NM_001304826.2		c.268_270delAACinsTCG	p.Asn90Ser	missense	N/A	NP_001291755.1
	TSACC	NM_001304818.2		c.214_216delAACinsTCG	p.Asn72Ser	missense	N/A	NP_001291747.1	Q96A04

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSACC	ENST00000368254.6	TSL:1 MANE Select	c.214_216delAACinsTCG	p.Asn72Ser	missense	N/A	ENSP00000357237.1	Q96A04
	TSACC	ENST00000368252.5	TSL:1	c.214_216delAACinsTCG	p.Asn72Ser	missense	N/A	ENSP00000357235.1	Q96A04
	TSACC	ENST00000368253.6	TSL:1	c.214_216delAACinsTCG	p.Asn72Ser	missense	N/A	ENSP00000357236.1	Q96A04

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

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: chr1-156316609;