rs544

Variant names:

• chr5-10264850-A-G
• rs544
• NM_012073.5:c.*67A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-10264850-A-G
• chr5-10264850-A-T
• chr5-10264850-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012073.5(CCT5):​c.*67A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,591,202 control chromosomes in the GnomAD database, including 549,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (43755 hom., cov: 32)
  • Exomes 𝑓: 0.83 (505382 hom.)
• Consequence: CCT5 NM_012073.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0910
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• hereditary sensory and autonomic neuropathy with spastic paraplegia

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CCT5-AS1 (HGNC:58210):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 5-10264850-A-G is Benign according to our data. Variant chr5-10264850-A-G is described in ClinVar as Benign. ClinVar VariationId is 350262.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012073.5. 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
	CCT5	NM_012073.5	MANE Select	c.*67A>G		3_prime_UTR	Exon 11 of 11	NP_036205.1	P48643-1
	CCT5	NM_001306153.1		c.*67A>G		3_prime_UTR	Exon 11 of 11	NP_001293082.1	B4DX08
	CCT5	NM_001306156.2		c.*67A>G		3_prime_UTR	Exon 11 of 11	NP_001293085.1	B7ZAR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCT5	ENST00000280326.9	TSL:1 MANE Select	c.*67A>G		3_prime_UTR	Exon 11 of 11	ENSP00000280326.4	P48643-1
	CCT5	ENST00000964556.1		c.*67A>G		3_prime_UTR	Exon 11 of 11	ENSP00000634615.1
	CCT5	ENST00000964554.1		c.*67A>G		3_prime_UTR	Exon 11 of 11	ENSP00000634613.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112372 AN: 152050 Hom.: 43738 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.866

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

GnomAD4 exome AF: 0.834 AC: 1200497 AN: 1439034 Hom.: 505382 Cov.: 25 AF XY: 0.830 AC XY: 595408 AN XY: 717164

African (AFR) AF: 0.448 AC: 14793 AN: 33032

American (AMR) AF: 0.801 AC: 35620 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 22573 AN: 25884

East Asian (EAS) AF: 0.890 AC: 35070 AN: 39414

South Asian (SAS) AF: 0.664 AC: 56622 AN: 85240

European-Finnish (FIN) AF: 0.862 AC: 45700 AN: 53016

Middle Eastern (MID) AF: 0.790 AC: 4388 AN: 5554

European-Non Finnish (NFE) AF: 0.857 AC: 936715 AN: 1092846

Other (OTH) AF: 0.823 AC: 49016 AN: 59576

GnomAD4 genome AF: 0.739 AC: 112429 AN: 152168 Hom.: 43755 Cov.: 32 AF XY: 0.742 AC XY: 55212 AN XY: 74396

African (AFR) AF: 0.466 AC: 19342 AN: 41490

American (AMR) AF: 0.809 AC: 12368 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3045 AN: 3472

East Asian (EAS) AF: 0.866 AC: 4485 AN: 5178

South Asian (SAS) AF: 0.664 AC: 3203 AN: 4822

European-Finnish (FIN) AF: 0.859 AC: 9096 AN: 10590

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58231 AN: 68008

Other (OTH) AF: 0.768 AC: 1623 AN: 2112

Alfa AF: 0.799 Hom.: 11093

Bravo AF: 0.728

Asia WGS AF: 0.773 AC: 2684 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary sensory and autonomic neuropathy with spastic paraplegia (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.055
DANN	Benign	0.66
PhyloP100		-0.091
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs544; hg19: chr5-10264962;