6-27293545-C-T

Variant summary

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

The ENST00000429945.1(POM121L2):c.217-7397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,822 control chromosomes in the GnomAD database, including 2,709 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 0.18 (2709 hom., cov: 31)
• Consequence: POM121L2 ENST00000429945.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

Genes affected

POM121L2 (HGNC:13973): (POM121 transmembrane nucleoporin like 2) Predicted to enable nuclear localization sequence binding activity. Predicted to be a structural constituent of nuclear pore. Predicted to be involved in RNA export from nucleus and protein import into nucleus. Predicted to be part of nuclear pore. [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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POM121L2	ENST00000429945.1	c.217-7397G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26712 AN: 151704 Hom.: 2709 Cov.: 31

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0599

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.176 AC: 26724 AN: 151822 Hom.: 2709 Cov.: 31 AF XY: 0.169 AC XY: 12504 AN XY: 74182

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0248

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0599

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.201

Alfa AF: 0.172 Hom.: 4802

Bravo AF: 0.186

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.77
Dann	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7746199; hg19: chr6-27261324;