rs145213207

Variant names:

• chr6-27309370-G-A
• rs145213207
• NM_033482.4:c.2801C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-27309370-G-A
• chr6-27309370-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_033482.4(POM121L2):​c.2801C>T​(p.Pro934Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,551,590 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: POM121L2 NM_033482.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.24
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029779434).
• BP6: Variant 6-27309370-G-A is Benign according to our data. Variant chr6-27309370-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2656313.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033482.4. 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
	POM121L2	NM_033482.4	MANE Select	c.2801C>T	p.Pro934Leu	missense	Exon 1 of 1	NP_258443.2	Q96KW2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POM121L2	ENST00000444565.2	TSL:6 MANE Select	c.2801C>T	p.Pro934Leu	missense	Exon 1 of 1	ENSP00000392726.1	Q96KW2
	POM121L2	ENST00000429945.1	TSL:3	c.216+1727C>T		intron	N/A	ENSP00000415181.1	H7C418

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000550 AC: 86 AN: 156412 AF XY: 0.000543

Gnomad AFR exome AF: 0.000505

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.000685

GnomAD4 exome AF: 0.00135 AC: 1884 AN: 1399298 Hom.: 1 Cov.: 31 AF XY: 0.00126 AC XY: 870 AN XY: 690162

African (AFR) AF: 0.000285 AC: 9 AN: 31594

American (AMR) AF: 0.0000840 AC: 3 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79216

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00166 AC: 1793 AN: 1078924

Other (OTH) AF: 0.00133 AC: 77 AN: 57998

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152292 Hom.: 1 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74482

African (AFR) AF: 0.000241 AC: 10 AN: 41544

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000796 Hom.: 0

Bravo AF: 0.000778

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00234 AC: 9

ExAC AF: 0.000277 AC: 7

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	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.2
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Benign	0.055
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Vest4		0.26
MVP		0.20
ClinPred		0.059	T
GERP RS		0.84
Varity_R		0.081
gMVP		0.093
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs145213207; hg19: chr6-27277149; COSMIC: COSV66276280;