rs201322182

Variant names:

• chr19-4446361-T-C
• rs201322182
• NM_025241.3:c.973A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_025241.3(UBXN6):​c.973A>G​(p.Lys325Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,572,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: UBXN6 NM_025241.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 3 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.108275324).

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.973A>G	p.Lys325Glu	missense	Exon 9 of 11	NP_079517.1	Q9BZV1-1
	UBXN6	NM_001171091.2		c.814A>G	p.Lys272Glu	missense	Exon 9 of 11	NP_001164562.1	Q9BZV1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBXN6	ENST00000301281.11	TSL:1 MANE Select	c.973A>G	p.Lys325Glu	missense	Exon 9 of 11	ENSP00000301281.5	Q9BZV1-1
	UBXN6	ENST00000394765.7	TSL:1	c.814A>G	p.Lys272Glu	missense	Exon 9 of 11	ENSP00000378246.2	Q9BZV1-2
	UBXN6	ENST00000950415.1		c.1075A>G	p.Lys359Glu	missense	Exon 9 of 11	ENSP00000620474.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152106 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000233 AC: 43 AN: 184160 AF XY: 0.000188

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000729

Gnomad ASJ exome AF: 0.000114

Gnomad EAS exome AF: 0.0000689

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000998

Gnomad OTH exome AF: 0.000615

GnomAD4 exome AF: 0.000176 AC: 250 AN: 1420572 Hom.: 1 Cov.: 32 AF XY: 0.000170 AC XY: 120 AN XY: 704892

African (AFR) AF: 0.0000609 AC: 2 AN: 32854

American (AMR) AF: 0.000624 AC: 25 AN: 40058

Ashkenazi Jewish (ASJ) AF: 0.0000393 AC: 1 AN: 25474

East Asian (EAS) AF: 0.000236 AC: 9 AN: 38064

South Asian (SAS) AF: 0.000603 AC: 50 AN: 82894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38380

Middle Eastern (MID) AF: 0.000872 AC: 5 AN: 5734

European-Non Finnish (NFE) AF: 0.000127 AC: 139 AN: 1097990

Other (OTH) AF: 0.000321 AC: 19 AN: 59124

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152106 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74314

African (AFR) AF: 0.0000724 AC: 3 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000332 Hom.: 0

Bravo AF: 0.000159

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000142 AC: 17

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.025	D
Polyphen		0.094	B
Vest4		0.48
MVP		0.50
MPC		0.062
ClinPred		0.11	T
GERP RS		2.0
Varity_R		0.27
gMVP		0.49
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs201322182; hg19: chr19-4446358;