7-72938609-C-T

Variant names:

• chr7-72938609-C-T
• NM_001387691.1:c.1295C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387691.1(POM121):​c.1295C>T​(p.Pro432Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: POM121 NM_001387691.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16932085).

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.1295C>T	p.Pro432Leu	missense	Exon 6 of 13	NP_001374620.1	Q96HA1-1
	POM121	NM_001387692.1		c.1295C>T	p.Pro432Leu	missense	Exon 6 of 12	NP_001374621.1
	POM121	NM_001257190.3		c.500C>T	p.Pro167Leu	missense	Exon 9 of 16	NP_001244119.1	Q96HA1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121	ENST00000434423.5	TSL:5 MANE Select	c.1295C>T	p.Pro432Leu	missense	Exon 6 of 13	ENSP00000405562.2	Q96HA1-1
	POM121	ENST00000395270.5	TSL:1	c.500C>T	p.Pro167Leu	missense	Exon 9 of 16	ENSP00000378687.1	Q96HA1-3
	POM121	ENST00000897647.1		c.1295C>T	p.Pro432Leu	missense	Exon 6 of 12	ENSP00000567706.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.053
Sift	Benign	0.071	T
Sift4G	Uncertain	0.0070	D
Polyphen		0.75	P
Vest4		0.23
MutPred		0.23		Loss of glycosylation at P432 (P = 0.0194)
MVP		0.12
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.37
gMVP		0.21
Mutation Taster		=94/6	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

hg19: chr7-72409148;