dbSNP rs1527047: ENSG00000257835:n.8A>G (chr12-77379769-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000552736.3(ENSG00000257835):n.8A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,934 control chromosomes in the GnomAD database, including 24,927 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24927 hom., cov: 31)

Exomes 𝑓: 0.43 ( 0 hom. )

Consequence

ENSG00000257835
ENST00000552736.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.678

Publications

1 publications found

Variant links:

Genes affected

ENSG00000257835 (HGNC:):

ENSG00000257835 links:

NAV3 (HGNC:15998): (neuron navigator 3) This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined. [provided by RefSeq, Jul 2008]

NAV3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

NAV3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902972	XR_007063383.1 link	n.1516A>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000257835	ENST00000552736.3 link	n.8A>G		non_coding_transcript_exon_variant	Exon 1 of 3	3
NAV3	ENST00000550042.2 link	c.-337+54555A>G		intron_variant	Intron 1 of 8	5		ENSP00000489639.1

Frequencies

GnomAD3 genomes

AF:

0.569

AC:

86337

AN:

151802

Hom.:

24931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.556

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.589

GnomAD4 exome

AF:

0.429

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.568

AC:

86354

AN:

151920

Hom.:

24927

Cov.:

AF XY:

0.561

AC XY:

41679

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.527

AC:

21806

AN:

41406

American (AMR)

AF:

0.546

AC:

8341

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.549

AC:

1907

AN:

3472

East Asian (EAS)

AF:

0.462

AC:

2376

AN:

5146

South Asian (SAS)

AF:

0.395

AC:

1903

AN:

4820

European-Finnish (FIN)

AF:

0.556

AC:

5859

AN:

10540

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.621

AC:

42220

AN:

67946

Other (OTH)

AF:

0.584

AC:

1236

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1872

3744

5616

7488

9360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.602

Hom.:

14121

Bravo

AF:

0.570

Asia WGS

AF:

0.456

AC:

1587

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.42

(source)

DANN

Benign

0.73

PhyloP100

-0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over