6-27308392-C-A

Position:

• chr6-27308392-C-A

Variant summary

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

The NM_033482.4(POM121L2):​c.*671G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151,514 control chromosomes in the GnomAD database, including 16,512 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 0.45 (16512 hom., cov: 33)
• Consequence: POM121L2 NM_033482.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POM121L2	NM_033482.4	c.*671G>T		3_prime_UTR_variant	1/1	ENST00000444565.2	NP_258443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POM121L2	ENST00000444565	c.*671G>T		3_prime_UTR_variant	1/1		NM_033482.4	ENSP00000392726.1
POM121L2	ENST00000429945.1	c.216+2705G>T		intron_variant		3		ENSP00000415181.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68387 AN: 151398 Hom.: 16500 Cov.: 33

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.452 AC: 68433 AN: 151514 Hom.: 16512 Cov.: 33 AF XY: 0.445 AC XY: 32965 AN XY: 74026

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.473

Alfa AF: 0.429 Hom.: 3866

Bravo AF: 0.464

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.50
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9366689; hg19: chr6-27276171;