21-29060618-G-A

Variant names:

• chr21-29060618-G-A
• rs1271224411
• NM_006585.4:c.1492C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006585.4(CCT8):​c.1492C>T​(p.Leu498Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCT8 NM_006585.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 1 publications found

Genes affected

CCT8 (HGNC:1623): (chaperonin containing TCP1 subunit 8) This gene encodes the theta subunit of the CCT chaperonin, which is abundant in the eukaryotic cytosol and may be involved in the transport and assembly of newly synthesized proteins. Alternative splicing results in multiple transcript variants of this gene. A pseudogene related to this gene is located on chromosome 1. [provided by RefSeq, Sep 2013]

CCT8 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.061).
• BP7: Synonymous conserved (PhyloP=0.706 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006585.4. 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
	CCT8	NM_006585.4	MANE Select	c.1492C>T	p.Leu498Leu	synonymous	Exon 14 of 15	NP_006576.2
	CCT8	NM_001282907.2		c.1435C>T	p.Leu479Leu	synonymous	Exon 15 of 16	NP_001269836.1	P50990-2
	CCT8	NM_001282908.2		c.1339C>T	p.Leu447Leu	synonymous	Exon 14 of 15	NP_001269837.1	Q7Z759

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT8	ENST00000286788.9	TSL:1 MANE Select	c.1492C>T	p.Leu498Leu	synonymous	Exon 14 of 15	ENSP00000286788.4	P50990-1
	CCT8	ENST00000470450.5	TSL:1	n.1566C>T		non_coding_transcript_exon	Exon 14 of 15
	CCT8	ENST00000936253.1		c.1486C>T	p.Leu496Leu	synonymous	Exon 14 of 15	ENSP00000606312.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.2
DANN	Benign	0.78
PhyloP100		0.71

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

Other links and lift over

dbSNP: rs1271224411; hg19: chr21-30432939;