rs236670

Variant names:

• chr7-75430050-T-G
• rs236670
• NM_001099415.3:c.481-3597A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000615331.5(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 ENST00000615331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412
• Publications: 8 publications found

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]

POM121C Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 22 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615331.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121C	NM_001099415.3	MANE Select	c.481-3597A>C		intron	N/A	NP_001092885.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121C	ENST00000615331.5	TSL:1 MANE Select	c.481-3597A>C		intron	N/A	ENSP00000481575.1
	POM121C	ENST00000607367.5	TSL:5	c.1207-3597A>C		intron	N/A	ENSP00000476236.2
	POM121C	ENST00000439629.2	TSL:5	c.97-3597A>C		intron	N/A	ENSP00000410033.1

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

African (AFR) AF: 0.00291 AC: 121 AN: 41568

American (AMR) AF: 0.00883 AC: 135 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.0146 AC: 76 AN: 5188

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4830

European-Finnish (FIN) AF: 0.0435 AC: 461 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1113 AN: 68016

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.0124 Hom.: 12

Bravo AF: 0.0102

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		0.41

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: rs236670; hg19: chr7-75059331;