5-52800830-C-T

Variant names:

• chr5-52800830-C-T
• NM_015946.5:c.436C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015946.5(PELO):​c.436C>T​(p.Leu146Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PELO NM_015946.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61

Genes affected

PELO (HGNC:8829): (pelota mRNA surveillance and ribosome rescue factor) This gene encodes a protein which contains a conserved nuclear localization signal. The encoded protein may have a role in spermatogenesis, cell cycle control, and in meiotic cell division. [provided by RefSeq, Jul 2008]

ITGA1 (HGNC:6134): (integrin subunit alpha 1) This gene encodes the alpha 1 subunit of integrin receptors. This protein heterodimerizes with the beta 1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. The alpha 1 subunit contains an inserted (I) von Willebrand factor type I domain which is thought to be involved in collagen binding. [provided by RefSeq, Jul 2008]

PELO-AS1 (HGNC:56263): (PELO antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PELO	NM_015946.5	c.436C>T	p.Leu146Phe	missense_variant	Exon 2 of 3	ENST00000274311.3	NP_057030.3
ITGA1	NM_181501.2	c.61+12416C>T		intron_variant	Intron 1 of 28	ENST00000282588.7	NP_852478.1
PELO-AS1	NR_186455.1	n.-17G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PELO	ENST00000274311.3	c.436C>T	p.Leu146Phe	missense_variant	Exon 2 of 3	1	NM_015946.5	ENSP00000274311.2
ITGA1	ENST00000282588.7	c.61+12416C>T		intron_variant	Intron 1 of 28	1	NM_181501.2	ENSP00000282588.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457644 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724700

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.436C>T (p.L146F) alteration is located in exon 2 (coding exon 1) of the PELO gene. This alteration results from a C to T substitution at nucleotide position 436, causing the leucine (L) at amino acid position 146 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.22
Sift	Benign	0.054	T
Sift4G	Uncertain	0.042	D
Polyphen		0.43	B
Vest4		0.64
MutPred		0.60		Loss of loop (P = 0.2237);
MVP		0.48
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.70
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-52096664;