NM_015946.5:c.233C>G

Variant names:

• chr5-52800627-C-G
• rs755880743
• NM_015946.5:c.233C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015946.5(PELO):​c.233C>G​(p.Ala78Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A78V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: PELO NM_015946.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.37
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2975331).

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.233C>G	p.Ala78Gly	missense	Exon 2 of 3	NP_057030.3
	ITGA1	NM_181501.2	MANE Select	c.61+12213C>G		intron	N/A	NP_852478.1	P56199
	PELO-AS1	NR_186455.1		n.122+65G>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.233C>G	p.Ala78Gly	missense	Exon 2 of 3	ENSP00000274311.2	Q9BRX2
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.61+12213C>G		intron	N/A	ENSP00000282588.5	P56199
	PELO	ENST00000901259.1		c.233C>G	p.Ala78Gly	missense	Exon 2 of 3	ENSP00000571318.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461624 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727108

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.0065	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.041
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.15
Sift	Benign	0.51	T
Sift4G	Benign	0.66	T
Polyphen		0.0070	B
Vest4		0.46
MutPred		0.58		Gain of sheet (P = 0.0149)
MVP		0.40
MPC		0.50
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.52
gMVP		0.45
Mutation Taster		=16/84	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: rs755880743; hg19: chr5-52096461;