Genetic Variant NM_012073.5:c.1498+191G>A (chr5-10263505-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012073.5(CCT5):c.1498+191G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,212 control chromosomes in the GnomAD database, including 43,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43709 hom., cov: 33)

Consequence

CCT5
NM_012073.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.20

Variant links:

Genes affected

CCT5 (HGNC:1618): (chaperonin containing TCP1 subunit 5) 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. Mutations in this gene cause hereditary sensory and autonomic neuropathy with spastic paraplegia (HSNSP). Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 5 and 13. [provided by RefSeq, Apr 2015]

CCT5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-10263505-G-A is Benign according to our data. Variant chr5-10263505-G-A is described in ClinVar as [Benign]. Clinvar id is 1257274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCT5	NM_012073.5 link	c.1498+191G>A		intron_variant	Intron 10 of 10	ENST00000280326.9	NP_036205.1	P48643-1V9HW37

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCT5	ENST00000280326.9 link	c.1498+191G>A		intron_variant	Intron 10 of 10	1	NM_012073.5	ENSP00000280326.4		P48643-1

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112334

AN:

152094

Hom.:

43692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.837

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.877

Gnomad EAS

AF:

0.865

Gnomad SAS

AF:

0.664

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.856

Gnomad OTH

AF:

0.767

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

GnomAD4 genome

AF:

0.738

AC:

112391

AN:

152212

Hom.:

43709

Cov.:

AF XY:

0.742

AC XY:

55192

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.466

Gnomad4 AMR

AF:

0.809

Gnomad4 ASJ

AF:

0.877

Gnomad4 EAS

AF:

0.866

Gnomad4 SAS

AF:

0.664

Gnomad4 FIN

AF:

0.859

Gnomad4 NFE

AF:

0.856

Gnomad4 OTH

AF:

0.769

Alfa

AF:

0.787

Hom.:

7933

Bravo

AF:

0.727

Asia WGS

AF:

0.773

AC:

2686

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.21

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over