rs12302873

Variant names:

• chr12-43752776-G-T
• rs12302873
• NM_031292.5:c.910+1560C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031292.5(PUS7L):​c.910+1560C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,044 control chromosomes in the GnomAD database, including 4,123 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 0.19 (4123 hom., cov: 32)
• Consequence: PUS7L NM_031292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031292.5. 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
	PUS7L	NM_031292.5	MANE Select	c.910+1560C>A		intron	N/A	NP_112582.3
	PUS7L	NM_001098614.3		c.910+1560C>A		intron	N/A	NP_001092084.1	Q9H0K6-1
	PUS7L	NM_001098615.2		c.910+1560C>A		intron	N/A	NP_001092085.1	Q9H0K6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUS7L	ENST00000344862.10	TSL:1 MANE Select	c.910+1560C>A		intron	N/A	ENSP00000343081.5	Q9H0K6-1
	PUS7L	ENST00000416848.6	TSL:1	c.910+1560C>A		intron	N/A	ENSP00000415899.2	Q9H0K6-1
	PUS7L	ENST00000551923.5	TSL:1	c.910+1560C>A		intron	N/A	ENSP00000447706.1	Q9H0K6-1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29044 AN: 151926 Hom.: 4110 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.191 AC: 29087 AN: 152044 Hom.: 4123 Cov.: 32 AF XY: 0.188 AC XY: 13971 AN XY: 74316

African (AFR) AF: 0.404 AC: 16720 AN: 41428

American (AMR) AF: 0.153 AC: 2334 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 595 AN: 3470

East Asian (EAS) AF: 0.0954 AC: 494 AN: 5178

South Asian (SAS) AF: 0.110 AC: 532 AN: 4820

European-Finnish (FIN) AF: 0.0937 AC: 991 AN: 10572

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6922 AN: 67976

Other (OTH) AF: 0.174 AC: 368 AN: 2112

Alfa AF: 0.147 Hom.: 887

Bravo AF: 0.205

Asia WGS AF: 0.132 AC: 457 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs12302873; hg19: chr12-44146579;