rs1870765

Positions:

• chr12-43753688-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031292.5(PUS7L):​c.910+648T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,290 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.018 (57 hom., cov: 32)
• Consequence: PUS7L NM_031292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382

Genes affected

PUS7L (HGNC:25276): (pseudouridine synthase 7 like) Predicted to enable pseudouridine synthase activity. Predicted to be involved in pseudouridine synthesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PUS7L	NM_031292.5	c.910+648T>G		intron_variant		ENST00000344862.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PUS7L	ENST00000344862.10	c.910+648T>G		intron_variant		1	NM_031292.5	P1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2815 AN: 152172 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.00396

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.0719

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0184 AC: 2809 AN: 152290 Hom.: 57 Cov.: 32 AF XY: 0.0193 AC XY: 1435 AN XY: 74454

Gnomad4 AFR AF: 0.00394

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.0390

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0191 Hom.: 4

Bravo AF: 0.0189

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs1870765; hg19: chr12-44147491;