NM_014396.4:c.717+30G>A

Variant names:

• chr7-38795435-C-T
• rs11984145
• NM_014396.4:c.717+30G>A

Variant summary

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

Score: -14 - Benign

-14

BP4_StrongBP6_ModerateBA1

The NM_014396.4(VPS41):​c.717+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 1,597,732 control chromosomes in the GnomAD database, including 3,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (312 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3066 hom.)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.96
• Publications: 12 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=-0.96).
• BP6: Variant 7-38795435-C-T is Benign according to our data. Variant chr7-38795435-C-T is described in ClinVar as [Benign]. Clinvar id is 1181871.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS41	NM_014396.4	c.717+30G>A		intron_variant	Intron 9 of 28	ENST00000310301.9	NP_055211.2
VPS41	NM_080631.4	c.642+30G>A		intron_variant	Intron 8 of 27		NP_542198.2
VPS41	XR_007060008.1	n.734+30G>A		intron_variant	Intron 9 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS41	ENST00000310301.9	c.717+30G>A		intron_variant	Intron 9 of 28	1	NM_014396.4	ENSP00000309457.4

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9515 AN: 152140 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0445

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.0679

GnomAD2 exomes AF: 0.0531 AC: 12687 AN: 238862 AF XY: 0.0528

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.0342

Gnomad ASJ exome AF: 0.0719

Gnomad EAS exome AF: 0.000166

Gnomad FIN exome AF: 0.0749

Gnomad NFE exome AF: 0.0669

Gnomad OTH exome AF: 0.0570

GnomAD4 exome AF: 0.0617 AC: 89114 AN: 1445474 Hom.: 3066 Cov.: 30 AF XY: 0.0606 AC XY: 43520 AN XY: 718294

African (AFR) AF: 0.0734 AC: 2425 AN: 33016

American (AMR) AF: 0.0369 AC: 1599 AN: 43366

Ashkenazi Jewish (ASJ) AF: 0.0682 AC: 1707 AN: 25042

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39424

South Asian (SAS) AF: 0.0260 AC: 2173 AN: 83708

European-Finnish (FIN) AF: 0.0709 AC: 3742 AN: 52786

Middle Eastern (MID) AF: 0.0750 AC: 425 AN: 5664

European-Non Finnish (NFE) AF: 0.0667 AC: 73516 AN: 1102768

Other (OTH) AF: 0.0590 AC: 3522 AN: 59700

GnomAD4 genome AF: 0.0625 AC: 9517 AN: 152258 Hom.: 312 Cov.: 32 AF XY: 0.0619 AC XY: 4611 AN XY: 74450

African (AFR) AF: 0.0745 AC: 3097 AN: 41554

American (AMR) AF: 0.0444 AC: 679 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0266 AC: 128 AN: 4820

European-Finnish (FIN) AF: 0.0755 AC: 802 AN: 10618

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0637 AC: 4335 AN: 68006

Other (OTH) AF: 0.0672 AC: 142 AN: 2112

Alfa AF: 0.0605 Hom.: 779

Bravo AF: 0.0614

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0060
DANN	Benign	0.59
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11984145; hg19: chr7-38835035;