rs741923

Variant names:

• chr19-4448846-G-A
• rs741923
• NM_025241.3:c.442-431C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 9 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]

ENSG00000280239 (HGNC:):

ACMG classification

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.

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.442-431C>T		intron	N/A	NP_079517.1	Q9BZV1-1
	UBXN6	NM_001171091.2		c.283-431C>T		intron	N/A	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.442-431C>T		intron	N/A	ENSP00000301281.5	Q9BZV1-1
	UBXN6	ENST00000394765.7	TSL:1	c.283-431C>T		intron	N/A	ENSP00000378246.2	Q9BZV1-2
	UBXN6	ENST00000950415.1		c.442-431C>T		intron	N/A	ENSP00000620474.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54147 AN: 152000 Hom.: 10065 Cov.: 33

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.: 0 AF XY: 0.412 AC XY: 9247 AN XY: 22434

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: 36 AN: 118

European-Non Finnish (NFE) AF: 0.446 AC: 10666 AN: 23924

Other (OTH) AF: 0.401 AC: 801 AN: 1996

GnomAD4 genome AF: 0.356 AC: 54155 AN: 152118 Hom.: 10067 Cov.: 33 AF XY: 0.356 AC XY: 26469 AN XY: 74348

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.60
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs741923; hg19: chr19-4448843;