rs236670

chr7-75430050-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001099415.3(POM121C):c.481-3597A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 152,286 control chromosomes in the GnomAD database, including 22 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 0.013 (22 hom., cov: 32)
• Consequence: POM121C NM_001099415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0132 (2010/152286) while in subpopulation NFE AF= 0.0164 (1113/68016). AF 95% confidence interval is 0.0156. There are 22 homozygotes in gnomad4. There are 1063 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POM121C	NM_001099415.3	c.481-3597A>C		intron_variant		ENST00000615331.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POM121C	ENST00000615331.5	c.481-3597A>C		intron_variant		1	NM_001099415.3	A2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2010 AN: 152168 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.00958

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

GnomAD4 genome AF: 0.0132 AC: 2010 AN: 152286 Hom.: 22 Cov.: 32 AF XY: 0.0143 AC XY: 1063 AN XY: 74480

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.0146

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0435

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.00948

Alfa AF: 0.0136 Hom.: 6

Bravo AF: 0.0102

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.74

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: rs236670; hg19: chr7-75059331;