chr5-52801814-G-A

Position:

• chr5-52801814-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015946.5(PELO):​c.1132G>A​(p.Gly378Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PELO NM_015946.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063714534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PELO	NM_015946.5	c.1132G>A	p.Gly378Ser	missense_variant	3/3	ENST00000274311.3
ITGA1	NM_181501.2	c.61+13400G>A		intron_variant		ENST00000282588.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PELO	ENST00000274311.3	c.1132G>A	p.Gly378Ser	missense_variant	3/3	1	NM_015946.5	P1
ITGA1	ENST00000282588.7	c.61+13400G>A		intron_variant		1	NM_181501.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458410 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725244

Gnomad4 AFR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.1132G>A (p.G378S) alteration is located in exon 3 (coding exon 2) of the PELO gene. This alteration results from a G to A substitution at nucleotide position 1132, causing the glycine (G) at amino acid position 378 to be replaced by a serine (S). 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	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.075
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.069
Sift	Benign	0.91	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.25		Gain of phosphorylation at G378 (P = 0.0033);
MVP		0.49
MPC		0.48
ClinPred		0.35	T
GERP RS		3.9
Varity_R		0.048
gMVP		0.20

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: chr5-52097648;