chr12-43753688-A-C

Variant names:

• chr12-43753688-A-C
• rs1870765
• NM_031292.5:c.910+648T>G

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+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
• Publications: 4 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=-0.9).
• 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 rank	MANE	Protein	UniProt
PUS7L	NM_031292.5	c.910+648T>G		intron_variant	Intron 2 of 8	ENST00000344862.10	NP_112582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PUS7L	ENST00000344862.10	c.910+648T>G		intron_variant	Intron 2 of 8	1	NM_031292.5	ENSP00000343081.5

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

African (AFR) AF: 0.00394 AC: 164 AN: 41572

American (AMR) AF: 0.0439 AC: 671 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 24 AN: 3472

East Asian (EAS) AF: 0.0390 AC: 202 AN: 5184

South Asian (SAS) AF: 0.0711 AC: 343 AN: 4822

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0180 AC: 1222 AN: 68018

Other (OTH) AF: 0.0218 AC: 46 AN: 2112

Alfa AF: 0.0205 Hom.: 13

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
PhyloP100		-0.38
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: rs1870765; hg19: chr12-44147491;