Genetic Variant NAXD:c.46+66C>T (chr13-110615713-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018210.4(NAXD):c.39C>T(p.Gly13Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,515,588 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 23 hom., cov: 33)

Exomes 𝑓: 0.00076 ( 18 hom. )

Consequence

NAXD
NM_018210.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.562

Publications

0 publications found

Variant links:

Genes affected

NAXD (HGNC:25576): (NAD(P)HX dehydratase) Enables ATP-dependent NAD(P)H-hydrate dehydratase activity. Predicted to be involved in metabolite repair. Predicted to be located in cytosol; endoplasmic reticulum; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

NAXD links:

NAXD-AS1 (HGNC:56341): (NAXD antisense RNA 1)

NAXD-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 13-110615713-C-T is Benign according to our data. Variant chr13-110615713-C-T is described in ClinVar as Benign. ClinVar VariationId is 1165481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.562 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0084 (1278/152096) while in subpopulation AFR AF = 0.0291 (1209/41498). AF 95% confidence interval is 0.0278. There are 23 homozygotes in GnomAd4. There are 580 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 23 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018210.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAXD	NM_001242882.2	MANE Select	c.46+66C>T		intron	N/A	NP_001229811.1	A0A7P0T9D8
NAXD	NM_018210.4		c.39C>T	p.Gly13Gly	synonymous	Exon 1 of 10	NP_060680.2	Q8IW45-2
NAXD	NM_001242881.2		c.39C>T	p.Gly13Gly	synonymous	Exon 1 of 10	NP_001229810.1	Q8IW45-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAXD	ENST00000680254.1	MANE Select	c.46+66C>T		intron	N/A	ENSP00000505619.1	A0A7P0T9D8
NAXD	ENST00000309957.3	TSL:2	c.39C>T	p.Gly13Gly	synonymous	Exon 1 of 10	ENSP00000311984.2	Q8IW45-2
NAXD	ENST00000680505.1		c.39C>T	p.Gly13Gly	synonymous	Exon 1 of 10	ENSP00000504986.1	Q8IW45-1

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1271

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00720

GnomAD2 exomes

AF:

0.00164

AC:

204

AN:

124584

AF XY:

0.00101

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.00132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000564

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000764

AC:

1042

AN:

1363492

Hom.:

Cov.:

AF XY:

0.000678

AC XY:

458

AN XY:

675456

show subpopulations

African (AFR)

AF:

0.0301

AC:

859

AN:

28494

American (AMR)

AF:

0.00141

AC:

AN:

33308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23794

East Asian (EAS)

AF:

0.00

AC:

AN:

30868

South Asian (SAS)

AF:

0.0000260

AC:

AN:

76950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37602

Middle Eastern (MID)

AF:

0.000897

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.0000168

AC:

AN:

1070444

Other (OTH)

AF:

0.00197

AC:

111

AN:

56458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

117

176

234

293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00840

AC:

1278

AN:

152096

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

580

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0291

AC:

1209

AN:

41498

American (AMR)

AF:

0.00307

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.000208

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

67984

Other (OTH)

AF:

0.00712

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00493

Hom.:

Bravo

AF:

0.00969

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

NAXD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.4

(source)

DANN

Benign

0.75

PhyloP100

0.56

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over