5-52800576-T-G

Variant names:

• chr5-52800576-T-G
• rs1326675266
• NM_015946.5:c.182T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015946.5(PELO):​c.182T>G​(p.Val61Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V61A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PELO NM_015946.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015946.5. 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
	PELO	NM_015946.5	MANE Select	c.182T>G	p.Val61Gly	missense	Exon 2 of 3	NP_057030.3
	ITGA1	NM_181501.2	MANE Select	c.61+12162T>G		intron	N/A	NP_852478.1	P56199
	PELO-AS1	NR_186455.1		n.122+116A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELO	ENST00000274311.3	TSL:1 MANE Select	c.182T>G	p.Val61Gly	missense	Exon 2 of 3	ENSP00000274311.2	Q9BRX2
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.61+12162T>G		intron	N/A	ENSP00000282588.5	P56199
	PELO	ENST00000901259.1		c.182T>G	p.Val61Gly	missense	Exon 2 of 3	ENSP00000571318.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.051	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		7.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.34
MutPred		0.77		Loss of stability (P = 0)
MVP		0.77
MPC		1.5
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.95
gMVP		0.80
Mutation Taster		=34/66	disease causing

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: rs1326675266; hg19: chr5-52096410;