rs1326675266

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-52800576-T-C
• chr5-52800576-T-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>C​(p.Val61Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PELO NM_015946.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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>C	p.Val61Ala	missense	Exon 2 of 3	NP_057030.3
	ITGA1	NM_181501.2	MANE Select	c.61+12162T>C		intron	N/A	NP_852478.1	P56199
	PELO-AS1	NR_186455.1		n.122+116A>G		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>C	p.Val61Ala	missense	Exon 2 of 3	ENSP00000274311.2	Q9BRX2
	ITGA1	ENST00000282588.7	TSL:1 MANE Select	c.61+12162T>C		intron	N/A	ENSP00000282588.5	P56199
	PELO	ENST00000901259.1		c.182T>C	p.Val61Ala	missense	Exon 2 of 3	ENSP00000571318.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461318 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 726936

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111704

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.0000241 AC: 1 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		7.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.78	P
Vest4		0.27
MutPred		0.74		Loss of stability (P = 2e-04)
MVP		0.65
MPC		1.1
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.59
gMVP		0.54
Mutation Taster		=49/51	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;