rs16897515

Positions:

• chr6-27310241-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2628 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21742 hom.)
• Consequence: POM121L2 NM_033482.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POM121L2	NM_033482.4	c.1930G>T	p.Gly644Cys	missense_variant	1/1	ENST00000444565.2	NP_258443.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POM121L2	ENST00000444565.2	c.1930G>T	p.Gly644Cys	missense_variant	1/1	6	NM_033482.4	ENSP00000392726.1
POM121L2	ENST00000429945.1	c.216+856G>T		intron_variant		3		ENSP00000415181.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26143 AN: 152094 Hom.: 2628 Cov.: 33

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

GnomAD3 exomes AF: 0.134 AC: 21357 AN: 158812 Hom.: 1709 AF XY: 0.136 AC XY: 11345 AN XY: 83674

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 SAS exome AF: 0.117

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.: 57 AF XY: 0.168 AC XY: 115777 AN XY: 690474

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0583

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.172 AC: 26155 AN: 152212 Hom.: 2628 Cov.: 33 AF XY: 0.164 AC XY: 12192 AN XY: 74402

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0529

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.199

Alfa AF: 0.174 Hom.: 1310

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	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.23	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Benign	0.043
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.039	D
Vest4		0.093
ClinPred		0.070	T
GERP RS		0.82
Varity_R		0.37
gMVP		0.18

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: rs16897515; hg19: chr6-27278020;