5-181244029-A-G

Variant names:

• chr5-181244029-A-G
• rs3756585
• ENST00000889840.1:c.-229T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000889840.1(RACK1):​c.-229T>C variant causes a 5 prime UTR premature start codon gain 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RACK1 ENST00000889840.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.54
• Publications: 11 publications found

Genes affected

RACK1 (HGNC:4399): (receptor for activated C kinase 1) Enables several functions, including cyclin binding activity; enzyme binding activity; and protein domain specific binding activity. Involved in several processes, including positive regulation of hydrolase activity; regulation of cellular protein metabolic process; and regulation of signal transduction. Located in several cellular components, including midbody; perinuclear region of cytoplasm; and phagocytic cup. Part of IRE1-RACK1-PP2A complex. [provided by Alliance of Genome Resources, Apr 2022]

RACK1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000889840.1. 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
	RACK1	NM_006098.5	MANE Select	c.-229T>C		upstream_gene	N/A	NP_006089.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RACK1	ENST00000889840.1		c.-229T>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000559899.1
	RACK1	ENST00000889840.1		c.-229T>C		5_prime_UTR	Exon 1 of 6	ENSP00000559899.1
	RACK1	ENST00000510199.5	TSL:3	c.254-1684T>C		intron	N/A	ENSP00000423569.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1239998 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 598014

African (AFR) AF: 0.00 AC: 0 AN: 27058

American (AMR) AF: 0.00 AC: 0 AN: 15784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17946

East Asian (EAS) AF: 0.00 AC: 0 AN: 31518

South Asian (SAS) AF: 0.00 AC: 0 AN: 57738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1007348

Other (OTH) AF: 0.00 AC: 0 AN: 51272

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.55
PhyloP100		-3.5
PromoterAI		-0.027	Neutral

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: rs3756585; hg19: chr5-180671029;