rs13224857

Variant names:

• chr7-38726749-C-T
• rs13224857
• NM_014396.4:c.2484+160G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014396.4(VPS41):​c.2484+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 152,236 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.086 (639 hom., cov: 33)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.244
• Publications: 0 publications found

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]

VPS41 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 29

  Inheritance: Unknown, AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive cerebellar ataxia-saccadic intrusion syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-38726749-C-T is Benign according to our data. Variant chr7-38726749-C-T is described in ClinVar as Benign. ClinVar VariationId is 1279808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014396.4. 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
	VPS41	NM_014396.4	MANE Select	c.2484+160G>A		intron	N/A	NP_055211.2	P49754-1
	VPS41	NM_080631.4		c.2409+160G>A		intron	N/A	NP_542198.2	P49754-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS41	ENST00000310301.9	TSL:1 MANE Select	c.2484+160G>A		intron	N/A	ENSP00000309457.4	P49754-1
	VPS41	ENST00000448833.5	TSL:1	n.*169+160G>A		intron	N/A	ENSP00000391980.1	H7BZX6
	VPS41	ENST00000951460.1		c.2580+160G>A		intron	N/A	ENSP00000621519.1

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13112 AN: 152118 Hom.: 636 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0858

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.0796

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.0746

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0863 AC: 13135 AN: 152236 Hom.: 639 Cov.: 33 AF XY: 0.0860 AC XY: 6405 AN XY: 74460

African (AFR) AF: 0.109 AC: 4517 AN: 41526

American (AMR) AF: 0.0593 AC: 907 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 298 AN: 3472

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5188

South Asian (SAS) AF: 0.131 AC: 635 AN: 4830

European-Finnish (FIN) AF: 0.0841 AC: 891 AN: 10596

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0821 AC: 5585 AN: 68014

Other (OTH) AF: 0.0734 AC: 155 AN: 2112

Alfa AF: 0.0933 Hom.: 116

Bravo AF: 0.0809

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.24
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: rs13224857; hg19: chr7-38766349;