6-27309808-T-C

Variant names:

• chr6-27309808-T-C
• NM_033482.4:c.2363A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033482.4(POM121L2):​c.2363A>G​(p.Gln788Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POM121L2 NM_033482.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.628

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16023496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POM121L2	NM_033482.4	c.2363A>G	p.Gln788Arg	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.2363A>G	p.Gln788Arg	missense_variant	Exon 1 of 1	6	NM_033482.4	ENSP00000392726.1
POM121L2	ENST00000429945.1	c.216+1289A>G		intron_variant	Intron 1 of 1	3		ENSP00000415181.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2363A>G (p.Q788R) alteration is located in exon 1 (coding exon 1) of the POM121L2 gene. This alteration results from a A to G substitution at nucleotide position 2363, causing the glutamine (Q) at amino acid position 788 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.049
Sift	Benign	0.057	T
Sift4G	Benign	0.062	T
Vest4		0.087
MutPred		0.15		Gain of methylation at Q788 (P = 0.0427);
MVP		0.072
ClinPred		0.16	T
GERP RS		2.5
Varity_R		0.044
gMVP		0.039

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-27277587;