rs533967943

Variant names:

• chr7-72926449-C-A
• rs533967943
• NM_001387691.1:c.832C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-72926449-C-A
• chr7-72926449-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001387691.1(POM121):​c.832C>A​(p.Pro278Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P278S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: POM121 NM_001387691.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

Genes affected

POM121 (HGNC:19702): (POM121 transmembrane nucleoporin) This gene encodes a transmembrane protein that localizes to the inner nuclear membrane and forms a core component of the nuclear pore complex, which mediates transport to and from the nucleus. The encoded protein may anchor this complex to the nuclear envelope. There are multiple related genes and pseudogenes for this gene on chromosomes 5, 7, 15, and 22. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387691.1. 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
	POM121	NM_001387691.1	MANE Select	c.832C>A	p.Pro278Thr	missense	Exon 2 of 13	NP_001374620.1	Q96HA1-1
	POM121	NM_001387692.1		c.832C>A	p.Pro278Thr	missense	Exon 2 of 12	NP_001374621.1
	POM121	NM_001387693.1		c.832C>A	p.Pro278Thr	missense	Exon 2 of 10	NP_001374622.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121	ENST00000434423.5	TSL:5 MANE Select	c.832C>A	p.Pro278Thr	missense	Exon 2 of 13	ENSP00000405562.2	Q96HA1-1
	POM121	ENST00000395270.5	TSL:1	c.37C>A	p.Pro13Thr	missense	Exon 5 of 16	ENSP00000378687.1	Q96HA1-3
	POM121	ENST00000897647.1		c.832C>A	p.Pro278Thr	missense	Exon 2 of 12	ENSP00000567706.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251112 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461672 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74460

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.066	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.037	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.26		Gain of phosphorylation at P278 (P = 0.0203)
MVP		0.25
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.36
gMVP		0.50
Mutation Taster		=71/29	polymorphism

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: rs533967943; hg19: chr7-72396987;