7-72926449-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387691.1(POM121):​c.832C>T​(p.Pro278Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POM121 NM_001387691.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POM121	NM_001387691.1	c.832C>T	p.Pro278Ser	missense_variant	Exon 2 of 13	ENST00000434423.5	NP_001374620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POM121	ENST00000434423.5	c.832C>T	p.Pro278Ser	missense_variant	Exon 2 of 13	5	NM_001387691.1	ENSP00000405562.2
POM121	ENST00000395270.5	c.37C>T	p.Pro13Ser	missense_variant	Exon 5 of 16	1		ENSP00000378687.1
POM121	ENST00000627934.3	c.37C>T	p.Pro13Ser	missense_variant	Exon 4 of 15	5		ENSP00000486504.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.37C>T (p.P13S) alteration is located in exon 4 (coding exon 1) of the POM121 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the proline (P) at amino acid position 13 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;.;.;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;D;D;.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.61	D;D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.4	.;.;.;.;M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.2	D;.;D;D;D
REVEL	Benign	0.28
Sift	Benign	0.050	D;.;D;T;D
Sift4G	Benign	0.13	T;D;T;D;T
Polyphen		1.0	.;.;.;.;D
Vest4		0.72
MutPred		0.24		.;.;.;.;Gain of phosphorylation at P278 (P = 0.023);
MVP		0.22
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.21
gMVP		0.49

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: rs533967943; hg19: chr7-72396987;