chr7-38726949-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014396.4(VPS41):​c.2444G>A​(p.Arg815Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000214 in 1,590,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

VPS41
NM_014396.4 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS41NM_014396.4 linkc.2444G>A p.Arg815Gln missense_variant Exon 28 of 29 ENST00000310301.9 NP_055211.2 P49754-1
VPS41NM_080631.4 linkc.2369G>A p.Arg790Gln missense_variant Exon 27 of 28 NP_542198.2 P49754-3
VPS41XM_017011988.2 linkc.1289G>A p.Arg430Gln missense_variant Exon 15 of 16 XP_016867477.1
VPS41XR_007060008.1 linkn.2555G>A non_coding_transcript_exon_variant Exon 29 of 29

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS41ENST00000310301.9 linkc.2444G>A p.Arg815Gln missense_variant Exon 28 of 29 1 NM_014396.4 ENSP00000309457.4 P49754-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152108
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000386
AC:
9
AN:
232934
Hom.:
0
AF XY:
0.0000474
AC XY:
6
AN XY:
126462
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000976
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000357
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000469
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000222
AC:
32
AN:
1438482
Hom.:
0
Cov.:
30
AF XY:
0.0000252
AC XY:
18
AN XY:
715326
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000718
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000361
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000227
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152226
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000302
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2444G>A (p.R815Q) alteration is located in exon 28 (coding exon 28) of the VPS41 gene. This alteration results from a G to A substitution at nucleotide position 2444, causing the arginine (R) at amino acid position 815 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.038
T;.
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Benign
0.058
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.8
L;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.27
Sift
Benign
0.23
T;T
Sift4G
Benign
0.067
T;T
Polyphen
0.99
D;.
Vest4
0.79
MVP
0.85
MPC
0.74
ClinPred
0.39
T
GERP RS
5.5
Varity_R
0.22
gMVP
0.66

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

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

Other links and lift over

dbSNP: rs149584623; hg19: chr7-38766549; API