Genetic Variant UBXN6:c.442-431C>T (chr19-4448846-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_025241.3(UBXN6):c.442-431C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 193,562 control chromosomes in the GnomAD database, including 13,765 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 0.36 ( 10067 hom., cov: 33)

Exomes 𝑓: 0.41 ( 3698 hom. )

Consequence

UBXN6
NM_025241.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.85

Publications

9 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:

ENSG00000280239 (HGNC:):

ENSG00000280239 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBXN6	NM_025241.3 link	c.442-431C>T		intron_variant	Intron 4 of 10	ENST00000301281.11	NP_079517.1	Q9BZV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBXN6	ENST00000301281.11 link	c.442-431C>T		intron_variant	Intron 4 of 10	1	NM_025241.3	ENSP00000301281.5		Q9BZV1-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54147

AN:

152000

Hom.:

10065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.302

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.337

GnomAD4 exome

AF:

0.410

AC:

16991

AN:

41444

Hom.:

3698

Cov.:

AF XY:

0.412

AC XY:

9247

AN XY:

22434

show subpopulations

African (AFR)

AF:

0.274

AC:

348

AN:

1268

American (AMR)

AF:

0.221

AC:

730

AN:

3308

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

350

AN:

846

East Asian (EAS)

AF:

0.320

AC:

639

AN:

1998

South Asian (SAS)

AF:

0.424

AC:

2880

AN:

6800

European-Finnish (FIN)

AF:

0.456

AC:

541

AN:

1186

Middle Eastern (MID)

AF:

0.305

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.446

AC:

10666

AN:

23924

Other (OTH)

AF:

0.401

AC:

801

AN:

1996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

473

946

1418

1891

2364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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:

0.356

AC:

54155

AN:

152118

Hom.:

10067

Cov.:

AF XY:

0.356

AC XY:

26469

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.265

AC:

11006

AN:

41504

American (AMR)

AF:

0.240

AC:

3668

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

1361

AN:

3468

East Asian (EAS)

AF:

0.301

AC:

1551

AN:

5154

South Asian (SAS)

AF:

0.391

AC:

1884

AN:

4818

European-Finnish (FIN)

AF:

0.455

AC:

4819

AN:

10598

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.422

AC:

28681

AN:

67986

Other (OTH)

AF:

0.338

AC:

713

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1799

3598

5398

7197

8996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.393

Hom.:

39039

Bravo

AF:

0.335

Asia WGS

AF:

0.317

AC:

1104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.60

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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