chr7-72925128-C-T

Variant names:

• chr7-72925128-C-T
• rs559447703
• NM_001387691.1:c.7C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001387691.1(POM121):​c.7C>T​(p.Pro3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,430,538 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (8 hom.)
• Consequence: POM121 NM_001387691.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28
• Publications: 1 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]

ENSG00000272843 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007335216).
• BP6: Variant 7-72925128-C-T is Benign according to our data. Variant chr7-72925128-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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.7C>T	p.Pro3Ser	missense	Exon 1 of 13	NP_001374620.1	Q96HA1-1
	POM121	NM_001387692.1		c.7C>T	p.Pro3Ser	missense	Exon 1 of 12	NP_001374621.1
	POM121	NM_001387693.1		c.7C>T	p.Pro3Ser	missense	Exon 1 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.7C>T	p.Pro3Ser	missense	Exon 1 of 13	ENSP00000405562.2	Q96HA1-1
	POM121	ENST00000395270.5	TSL:1	c.-151-1134C>T		intron	N/A	ENSP00000378687.1	Q96HA1-3
	POM121	ENST00000897647.1		c.7C>T	p.Pro3Ser	missense	Exon 1 of 12	ENSP00000567706.1

Frequencies

GnomAD3 genomes AF: 0.000677 AC: 103 AN: 152120 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00287 AC: 90 AN: 31354 AF XY: 0.00210

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00108

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00108

GnomAD4 exome AF: 0.000275 AC: 352 AN: 1278302 Hom.: 8 Cov.: 30 AF XY: 0.000268 AC XY: 168 AN XY: 627954

African (AFR) AF: 0.000241 AC: 6 AN: 24856

American (AMR) AF: 0.0138 AC: 220 AN: 16000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19338

East Asian (EAS) AF: 0.0000343 AC: 1 AN: 29186

South Asian (SAS) AF: 0.000895 AC: 57 AN: 63676

European-Finnish (FIN) AF: 0.000641 AC: 20 AN: 31216

Middle Eastern (MID) AF: 0.000794 AC: 3 AN: 3776

European-Non Finnish (NFE) AF: 0.0000241 AC: 25 AN: 1037268

Other (OTH) AF: 0.000377 AC: 20 AN: 52986

GnomAD4 genome AF: 0.000677 AC: 103 AN: 152236 Hom.: 1 Cov.: 32 AF XY: 0.000766 AC XY: 57 AN XY: 74436

African (AFR) AF: 0.000241 AC: 10 AN: 41578

American (AMR) AF: 0.00510 AC: 78 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67968

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.00122

ExAC AF: 0.000598 AC: 8

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0070	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.25
MutPred		0.13		Gain of phosphorylation at P3 (P = 0.0063)
MVP		0.13
ClinPred		0.22	T
GERP RS		3.8
PromoterAI		0.023	Neutral
Varity_R		0.35
Mutation Taster		=90/10	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: rs559447703; hg19: chr7-72395666;