NM_014396.4:c.*1170G>A

Variant names:

• chr7-38725076-C-T
• rs11773094
• NM_014396.4:c.*1170G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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.

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.*1170G>A		3_prime_UTR	Exon 29 of 29	NP_055211.2	P49754-1
	VPS41	NM_080631.4		c.*1170G>A		3_prime_UTR	Exon 28 of 28	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.*1170G>A		3_prime_UTR	Exon 29 of 29	ENSP00000309457.4	P49754-1
	VPS41	ENST00000951459.1		c.*1170G>A		3_prime_UTR	Exon 29 of 29	ENSP00000621518.1
	VPS41	ENST00000862386.1		c.*1170G>A		3_prime_UTR	Exon 29 of 29	ENSP00000532445.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.542 AC: 13 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.115 AC: 4793 AN: 41514

American (AMR) AF: 0.221 AC: 3379 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3472

East Asian (EAS) AF: 0.114 AC: 590 AN: 5172

South Asian (SAS) AF: 0.151 AC: 726 AN: 4822

European-Finnish (FIN) AF: 0.421 AC: 4452 AN: 10578

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27681 AN: 67966

Other (OTH) AF: 0.275 AC: 581 AN: 2116

Alfa AF: 0.347 Hom.: 13215

Bravo AF: 0.266

Asia WGS AF: 0.117 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.085
DANN	Benign	0.56
PhyloP100		-2.3
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: rs11773094; hg19: chr7-38764676;