rs11773094

Positions:

• chr7-38725076-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014396.4(VPS41):​c.*1170G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,156 control chromosomes in the GnomAD database, including 7,768 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 0.29 (7766 hom., cov: 33)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: VPS41 NM_014396.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

Genes affected

VPS41 (HGNC:12713): (VPS41 subunit of HOPS complex) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human ortholog of yeast Vps41 protein which is also conserved in Drosophila, tomato, and Arabidopsis. Expression studies in yeast and human indicate that this protein may be involved in the formation and fusion of transport vesicles from the Golgi. Several transcript variants encoding different isoforms have been described for this gene, however, the full-length nature of not all is known. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.*1170G>A		3_prime_UTR_variant	29/29	ENST00000310301.9
VPS41	NM_080631.4	c.*1170G>A		3_prime_UTR_variant	28/28
VPS41	XM_017011988.2	c.*1170G>A		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.*1170G>A		3_prime_UTR_variant	29/29	1	NM_014396.4	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43823 AN: 152012 Hom.: 7766 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.500 AC: 13 AN: 26 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 10 AN XY: 20

Gnomad4 NFE exome AF: 0.542

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.288 AC: 43818 AN: 152130 Hom.: 7766 Cov.: 33 AF XY: 0.285 AC XY: 21191 AN XY: 74368

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.275

Alfa AF: 0.358 Hom.: 10744

Bravo AF: 0.266

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.085
DANN	Benign	0.56

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: rs11773094; hg19: chr7-38764676;