9-88535571-C-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PP3_ModerateBP6_Moderate

The NM_001161625.2(NXNL2):c.137C>A(p.Pro46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,609,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NXNL2
NM_001161625.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.85

Variant links:

Genes affected

NXNL2 (HGNC:30482): (nucleoredoxin like 2) Predicted to be involved in photoreceptor cell maintenance and sensory perception. Predicted to act upstream of or within sensory perception of smell and visual perception. [provided by Alliance of Genome Resources, Apr 2022]

NXNL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.85

BP6

Variant 9-88535571-C-A is Benign according to our data. Variant chr9-88535571-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2615233.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXNL2	NM_001161625.2 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 1 of 2	ENST00000375854.8	NP_001155097.1	Q5VZ03-1
NXNL2	NM_145283.3 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 1 of 3		NP_660326.2	Q5VZ03-3
NXNL2	XM_011518276.3 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 1 of 2		XP_011516578.1
NXNL2	XM_005251727.4 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 1 of 2		XP_005251784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NXNL2	ENST00000375854.8 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 1 of 2	5	NM_001161625.2	ENSP00000365014.3	Q5VZ03-1
NXNL2	ENST00000375855.3 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 1 of 3	1		ENSP00000365015.3	Q5VZ03-3
NXNL2	ENST00000649870.2 link	c.137C>A	p.Pro46Gln	missense_variant	Exon 2 of 3			ENSP00000508470.1	Q5VZ03-1
NXNL2	ENST00000478686.1 link	n.386C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000842

AC:

AN:

237428

Hom.:

AF XY:

0.00

AC XY:

AN XY:

129984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457302

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 02, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.23

.;T;.

Eigen

Benign

-0.082

Eigen_PC

Benign

-0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

T;T;T

M_CAP

Pathogenic

0.59

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Uncertain

0.47

MutationAssessor

Pathogenic

3.3

.;M;M

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-7.8

.;D;D

REVEL

Uncertain

0.46

Sift

Uncertain

0.022

.;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0, 0.86

.;D;P

Vest4

0.35, 0.34

MutPred

0.77

Loss of phosphorylation at T45 (P = 0.0699);Loss of phosphorylation at T45 (P = 0.0699);Loss of phosphorylation at T45 (P = 0.0699);

MVP

0.86

MPC

1.7

ClinPred

0.98

GERP RS

2.1

Varity_R

0.40

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over