NM_001304817.2:c.175C>G

Variant names:

• chr1-156346779-C-G
• rs745316310
• NM_001304817.2:c.175C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001304817.2(TSACC):​c.175C>G​(p.Pro59Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,812 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P59S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (1 hom.)
• Consequence: TSACC NM_001304817.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2268539).

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.175C>G	p.Pro59Ala	missense	Exon 4 of 4	NP_001291746.1	Q96A04
	TSACC	NM_001304826.2		c.229C>G	p.Pro77Ala	missense	Exon 4 of 4	NP_001291755.1
	TSACC	NM_001304818.2		c.175C>G	p.Pro59Ala	missense	Exon 4 of 4	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.175C>G	p.Pro59Ala	missense	Exon 4 of 4	ENSP00000357237.1	Q96A04
	TSACC	ENST00000368252.5	TSL:1	c.175C>G	p.Pro59Ala	missense	Exon 4 of 4	ENSP00000357235.1	Q96A04
	TSACC	ENST00000368253.6	TSL:1	c.175C>G	p.Pro59Ala	missense	Exon 4 of 4	ENSP00000357236.1	Q96A04

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461812 Hom.: 1 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727218

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.037
Eigen_PC	Benign	0.033
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.23	T
PhyloP100		1.3
Sift4G	Benign	0.35	T
Vest4		0.31
MVP		0.15
ClinPred		0.88	D
GERP RS		2.4
Varity_R		0.13
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs745316310; hg19: chr1-156316570;