dbSNP rs16897515: POM121L2:p.Gly644Cys (chr6-27310241-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033482.4(POM121L2):c.1930G>T(p.Gly644Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,552,202 control chromosomes in the GnomAD database, including 24,370 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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. G644D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.17 ( 2628 hom., cov: 33)

Exomes 𝑓: 0.17 ( 21742 hom. )

Consequence

POM121L2
NM_033482.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.986

Publications

47 publications found

Variant links:

Genes affected

POM121L2 (HGNC:13973): (POM121 transmembrane nucleoporin like 2) Predicted to enable nuclear localization sequence binding activity. Predicted to be a structural constituent of nuclear pore. Predicted to be involved in RNA export from nucleus and protein import into nucleus. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

POM121L2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057967305).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POM121L2	NM_033482.4 link	c.1930G>T	p.Gly644Cys	missense_variant	Exon 1 of 1	ENST00000444565.2	NP_258443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POM121L2	ENST00000444565.2 link	c.1930G>T	p.Gly644Cys	missense_variant	Exon 1 of 1	6	NM_033482.4	ENSP00000392726.1
POM121L2	ENST00000429945.1 link	c.216+856G>T		intron_variant	Intron 1 of 1	3		ENSP00000415181.1

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26143

AN:

152094

Hom.:

2628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0529

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.201

GnomAD2 exomes

AF:

0.134

AC:

21357

AN:

158812

AF XY:

0.136

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.0232

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.170

AC:

237372

AN:

1399990

Hom.:

21742

Cov.:

AF XY:

0.168

AC XY:

115777

AN XY:

690474

show subpopulations

African (AFR)

AF:

0.248

AC:

7829

AN:

31600

American (AMR)

AF:

0.114

AC:

4083

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

4961

AN:

25182

East Asian (EAS)

AF:

0.0115

AC:

411

AN:

35740

South Asian (SAS)

AF:

0.120

AC:

9542

AN:

79234

European-Finnish (FIN)

AF:

0.0583

AC:

2889

AN:

49578

Middle Eastern (MID)

AF:

0.187

AC:

1065

AN:

5702

European-Non Finnish (NFE)

AF:

0.182

AC:

196602

AN:

1079060

Other (OTH)

AF:

0.172

AC:

9990

AN:

58188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

11894

23788

35682

47576

59470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7218

14436

21654

28872

36090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.172

AC:

26155

AN:

152212

Hom.:

2628

Cov.:

AF XY:

0.164

AC XY:

12192

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.242

AC:

10044

AN:

41530

American (AMR)

AF:

0.155

AC:

2365

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3470

East Asian (EAS)

AF:

0.0240

AC:

124

AN:

5168

South Asian (SAS)

AF:

0.114

AC:

549

AN:

4820

European-Finnish (FIN)

AF:

0.0529

AC:

561

AN:

10606

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.165

AC:

11190

AN:

68008

Other (OTH)

AF:

0.199

AC:

420

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1093

2187

3280

4374

5467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.168

Hom.:

4513

Bravo

AF:

0.183

TwinsUK

AF:

0.203

AC:

751

ALSPAC

AF:

0.189

AC:

730

ESP6500AA

AF:

0.250

AC:

346

ESP6500EA

AF:

0.181

AC:

577

ExAC

AF:

0.138

AC:

3566

Asia WGS

AF:

0.0820

AC:

287

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.99

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-6.2

REVEL

Benign

0.043

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.039

Vest4

0.093

ClinPred

0.070

GERP RS

0.82

Varity_R

0.37

gMVP

0.18

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over