Genetic Variant UBXN6:p.Asp345Asn (chr19-4446301-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025241.3(UBXN6):c.1033G>A(p.Asp345Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000014 in 1,571,142 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D345Y) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

Publications

0 publications found

Variant links:

Genes affected

UBXN6 (HGNC:14928): (UBX domain protein 6) Involved in ERAD pathway; endosome to lysosome transport via multivesicular body sorting pathway; and macroautophagy. Located in bounding membrane of organelle and cytosol. Is extrinsic component of membrane. Part of endosome and protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

UBXN6 links:

CHAF1A (HGNC:1910): (chromatin assembly factor 1 subunit A) Chromatin assembly factor I (CAF1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995 [PubMed 7600578]).[supplied by OMIM, Mar 2008]

CHAF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025241.3. 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
	UBXN6	NM_025241.3	MANE Select	c.1033G>A	p.Asp345Asn	missense	Exon 9 of 11	NP_079517.1	Q9BZV1-1
	UBXN6	NM_001171091.2		c.874G>A	p.Asp292Asn	missense	Exon 9 of 11	NP_001164562.1	Q9BZV1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBXN6	ENST00000301281.11	TSL:1 MANE Select	c.1033G>A	p.Asp345Asn	missense	Exon 9 of 11	ENSP00000301281.5	Q9BZV1-1
UBXN6	ENST00000394765.7	TSL:1	c.874G>A	p.Asp292Asn	missense	Exon 9 of 11	ENSP00000378246.2	Q9BZV1-2
UBXN6	ENST00000950415.1		c.1135G>A	p.Asp379Asn	missense	Exon 9 of 11	ENSP00000620474.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000540

AC:

AN:

185190

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1418806

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

703402

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32872

American (AMR)

AF:

0.00

AC:

AN:

39908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24966

East Asian (EAS)

AF:

0.000104

AC:

AN:

38354

South Asian (SAS)

AF:

0.0000122

AC:

AN:

82296

European-Finnish (FIN)

AF:

0.0000493

AC:

AN:

40562

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000730

AC:

AN:

1095278

Other (OTH)

AF:

0.0000340

AC:

AN:

58882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.0000197

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41582

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000333

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.1

PhyloP100

4.6

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Polyphen

1.0

Vest4

0.87

MVP

0.80

MPC

0.32

ClinPred

0.99

GERP RS

3.3

Varity_R

0.69

gMVP

0.83

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over