6-27309597-A-T

Variant names:

• chr6-27309597-A-T
• rs1172735385
• NM_033482.4:c.2574T>A

Variant summary

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

The NM_033482.4(POM121L2):​c.2574T>A​(p.Ser858Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POM121L2 NM_033482.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 0 publications found

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

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=0.12778038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POM121L2	NM_033482.4	c.2574T>A	p.Ser858Arg	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	c.2574T>A	p.Ser858Arg	missense_variant	Exon 1 of 1	6	NM_033482.4	ENSP00000392726.1
POM121L2	ENST00000429945.1	c.216+1500T>A		intron_variant	Intron 1 of 1	3		ENSP00000415181.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399450 Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2 AN XY: 690214

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078934

Other (OTH) AF: 0.00 AC: 0 AN: 58024

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.45
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.061
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.11	T
Vest4		0.23
MutPred		0.27		Loss of glycosylation at S858 (P = 0.0455);
MVP		0.055
ClinPred		0.85	D
GERP RS		-2.5
Varity_R		0.099
gMVP		0.32
Mutation Taster		=99/1	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: rs1172735385; hg19: chr6-27277376;