rs6974138

Positions:

• chr7-75434209-G-C

Variant summary

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

The NM_001099415.3(POM121C):​c.480+3306C>G 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 152,110 control chromosomes in the GnomAD database, including 2,691 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 (2691 hom., cov: 32)
• Consequence: POM121C NM_001099415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

Genes affected

POM121C (HGNC:34005): (POM121 transmembrane nucleoporin C) 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 located in nuclear envelope. 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POM121C	NM_001099415.3	c.480+3306C>G		intron_variant		ENST00000615331.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POM121C	ENST00000615331.5	c.480+3306C>G		intron_variant		1	NM_001099415.3	A2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26749 AN: 151992 Hom.: 2687 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.00596

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.176 AC: 26759 AN: 152110 Hom.: 2691 Cov.: 32 AF XY: 0.173 AC XY: 12896 AN XY: 74368

Gnomad4 AFR AF: 0.0986

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.00597

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.181

Alfa AF: 0.207 Hom.: 426

Bravo AF: 0.167

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.69

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: rs6974138; hg19: chr7-75063487;