Genetic Variant NM_025241.3:c.937C>G (chr19-4446397-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025241.3(UBXN6):c.937C>G(p.Arg313Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,426,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R313L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

UBXN6
NM_025241.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.35

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37735465).

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.937C>G	p.Arg313Gly	missense	Exon 9 of 11	NP_079517.1	Q9BZV1-1
	UBXN6	NM_001171091.2		c.778C>G	p.Arg260Gly	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.937C>G	p.Arg313Gly	missense	Exon 9 of 11	ENSP00000301281.5	Q9BZV1-1
UBXN6	ENST00000394765.7	TSL:1	c.778C>G	p.Arg260Gly	missense	Exon 9 of 11	ENSP00000378246.2	Q9BZV1-2
UBXN6	ENST00000950415.1		c.1039C>G	p.Arg347Gly	missense	Exon 9 of 11	ENSP00000620474.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1426220

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

708536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33024

American (AMR)

AF:

0.00

AC:

AN:

40988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25478

East Asian (EAS)

AF:

0.00

AC:

AN:

38554

South Asian (SAS)

AF:

0.00

AC:

AN:

83666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1101320

Other (OTH)

AF:

0.00

AC:

AN:

59350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

0.0035

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.041

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PhyloP100

5.3

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.14

Sift

Uncertain

0.0020

Sift4G

Benign

0.093

Polyphen

0.37

Vest4

0.53

MutPred

0.43

Loss of MoRF binding (P = 0.0469)

MVP

0.62

MPC

0.064

ClinPred

0.98

GERP RS

3.1

Varity_R

0.66

gMVP

0.36

Mutation Taster

=44/56

disease causing

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over