rs387740

Variant names:

• chr7-75416953-C-T
• rs387740
• NM_001099415.3:c.*1843G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099415.3(POM121C):​c.*1843G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POM121C NM_001099415.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 1 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]

NSUN5P1 (HGNC:):

NSUN5P1 (HGNC:19146): (NSUN5 pseudogene 1) This locus represents a transcribed pseudogene of a nearby locus on chromosome 7, which encodes a putative methyltransferase. There is also a third closely related pseudogene locus in this region. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099415.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121C	NM_001099415.3	MANE Select	c.*1843G>A		3_prime_UTR	Exon 15 of 15	NP_001092885.2	A8CG34-2
	NSUN5P1	NR_033322.3		n.*161C>T		downstream_gene	N/A
	NSUN5P1	NR_104013.1		n.*161C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121C	ENST00000615331.5	TSL:1 MANE Select	c.*1843G>A		3_prime_UTR	Exon 15 of 15	ENSP00000481575.1	A8CG34-2
	POM121C	ENST00000874767.1		c.*1843G>A		3_prime_UTR	Exon 16 of 16	ENSP00000544826.1
	POM121C	ENST00000874768.1		c.*1843G>A		3_prime_UTR	Exon 17 of 17	ENSP00000544827.1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152074 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000186 AC: 23 AN: 1237768 Hom.: 0 Cov.: 31 AF XY: 0.0000235 AC XY: 14 AN XY: 596306

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000728 AC: 2 AN: 27476

American (AMR) AF: 0.00 AC: 0 AN: 17878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18072

East Asian (EAS) AF: 0.00 AC: 0 AN: 32558

South Asian (SAS) AF: 0.0000538 AC: 3 AN: 55728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3462

European-Non Finnish (NFE) AF: 0.0000149 AC: 15 AN: 1005182

Other (OTH) AF: 0.0000588 AC: 3 AN: 51030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000279632), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000164 AC: 25 AN: 152192 Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16 AN XY: 74422

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000481 AC: 2 AN: 41542

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000253 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.9
DANN	Benign	0.89
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs387740; hg19: chr7-75046232;