Genetic Variant UBXN6:p.Ala268Ser (chr19-4446618-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is . The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025241.3(UBXN6):c.802G>T(p.Ala268Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. A268T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBXN6
NM_025241.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.65

Publications

4 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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: LiferaOmics

CHAF1A links:

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new If you want to explore the variant's impact on the transcript NM_025241.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.091).

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.802G>T	p.Ala268Ser	missense	Exon 8 of 11	NP_079517.1	Q9BZV1-1
	UBXN6	NM_001171091.2		c.643G>T	p.Ala215Ser	missense	Exon 8 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.802G>T	p.Ala268Ser	missense	Exon 8 of 11	ENSP00000301281.5	Q9BZV1-1
UBXN6	ENST00000394765.7	TSL:1	c.643G>T	p.Ala215Ser	missense	Exon 8 of 11	ENSP00000378246.2	Q9BZV1-2
UBXN6	ENST00000950415.1		c.904G>T	p.Ala302Ser	missense	Exon 8 of 11	ENSP00000620474.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

248260

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726376

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111774

Other (OTH)

AF:

0.00

AC:

AN:

60356

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

0.023

Eigen_PC

Benign

-0.025

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.064

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.7

PhyloP100

3.6

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

REVEL

Benign

0.091

Sift

Benign

0.11

Sift4G

Benign

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.083

gMVP

0.35

Mutation Taster

=85/15

polymorphism

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over