7-72926848-G-T

Variant names:

• chr7-72926848-G-T
• rs782242056
• NM_001387691.1:c.907G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387691.1(POM121):​c.907G>T​(p.Ala303Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A303T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POM121 NM_001387691.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055950165).

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.907G>T	p.Ala303Ser	missense	Exon 3 of 13	NP_001374620.1	Q96HA1-1
	POM121	NM_001387692.1		c.907G>T	p.Ala303Ser	missense	Exon 3 of 12	NP_001374621.1
	POM121	NM_001387693.1		c.907G>T	p.Ala303Ser	missense	Exon 3 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.907G>T	p.Ala303Ser	missense	Exon 3 of 13	ENSP00000405562.2	Q96HA1-1
	POM121	ENST00000395270.5	TSL:1	c.112G>T	p.Ala38Ser	missense	Exon 6 of 16	ENSP00000378687.1	Q96HA1-3
	POM121	ENST00000897647.1		c.907G>T	p.Ala303Ser	missense	Exon 3 of 12	ENSP00000567706.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461668 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727144

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: 0.00 AC: 0 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: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111838

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.96
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.013
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.035
Sift	Benign	0.66	T
Sift4G	Benign	0.37	T
Polyphen		0.39	B
Vest4		0.13
MutPred		0.13		Gain of phosphorylation at A303 (P = 0.0076)
MVP		0.014
ClinPred		0.17	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.16
Mutation Taster		=95/5	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: rs782242056; hg19: chr7-72397386;