Variant chr7-38726273-T-TCCTGGTCCACGGTTCTTAGCACTG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_014396.4(VPS41):c.2537_2538insCAGTGCTAAGAACCGTGGACCAGG(p.Ala840_Ser847dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.00195 in 1,614,002 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 11 hom. )

Consequence

VPS41
NM_014396.4 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.72

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_014396.4

BP6

Variant 7-38726273-T-TCCTGGTCCACGGTTCTTAGCACTG is Benign according to our data. Variant chr7-38726273-T-TCCTGGTCCACGGTTCTTAGCACTG is described in ClinVar as [Benign]. Clinvar id is 2359877.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VPS41	NM_014396.4 linkuse as main transcript	c.2537_2538insCAGTGCTAAGAACCGTGGACCAGG	p.Ala840_Ser847dup	inframe_insertion	29/29	ENST00000310301.9
VPS41	NM_080631.4 linkuse as main transcript	c.2462_2463insCAGTGCTAAGAACCGTGGACCAGG	p.Ala815_Ser822dup	inframe_insertion	28/28
VPS41	XM_017011988.2 linkuse as main transcript	c.1382_1383insCAGTGCTAAGAACCGTGGACCAGG	p.Ala455_Ser462dup	inframe_insertion	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9 linkuse as main transcript	c.2537_2538insCAGTGCTAAGAACCGTGGACCAGG	p.Ala840_Ser847dup	inframe_insertion	29/29	1	NM_014396.4	P1	P49754-1

Frequencies

GnomAD3 genomes

AF:

0.00212

AC:

322

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0162

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00237

AC:

589

AN:

248998

Hom.:

AF XY:

0.00242

AC XY:

326

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00193

AC:

2818

AN:

1461662

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1386

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000380

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000672

Gnomad4 FIN exome

AF:

0.0137

Gnomad4 NFE exome

AF:

0.00171

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.00211

AC:

322

AN:

152340

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

208

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0162

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00107

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 10, 2022

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over