rs741923

chr19-4448846-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UBXN6	NM_025241.3	c.442-431C>T		intron_variant		ENST00000301281.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBXN6	ENST00000301281.11	c.442-431C>T		intron_variant		1	NM_025241.3	P1
	ENST00000624986.1	n.37G>A		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.401

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.338

Alfa AF: 0.395 Hom.: 13088

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
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs741923; hg19: chr19-4448843;