chr7-38740075-C-T

Variant names:

• chr7-38740075-C-T
• rs2286103
• NM_014396.4:c.2259+1910G>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.2259+1910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 152,336 control chromosomes in the GnomAD database, including 75,103 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 0.99 (75103 hom., cov: 32)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS41	NM_014396.4	c.2259+1910G>A		intron_variant	Intron 25 of 28	ENST00000310301.9	NP_055211.2
VPS41	NM_080631.4	c.2184+1910G>A		intron_variant	Intron 24 of 27		NP_542198.2
VPS41	XM_017011988.2	c.1104+1910G>A		intron_variant	Intron 12 of 15		XP_016867477.1
VPS41	XR_007060008.1	n.2276+1910G>A		intron_variant	Intron 25 of 28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS41	ENST00000310301.9	c.2259+1910G>A		intron_variant	Intron 25 of 28	1	NM_014396.4	ENSP00000309457.4
VPS41	ENST00000448833.5	n.300+1910G>A		intron_variant	Intron 3 of 7	1		ENSP00000391980.1
VPS41	ENST00000395969.6	c.2184+1910G>A		intron_variant	Intron 24 of 27	5		ENSP00000379297.2
VPS41	ENST00000482217.1	n.718+1910G>A		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151141 AN: 152218 Hom.: 75041 Cov.: 32

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.983

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.982

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

GnomAD4 genome AF: 0.993 AC: 151262 AN: 152336 Hom.: 75103 Cov.: 32 AF XY: 0.993 AC XY: 73951 AN XY: 74486

African (AFR) AF: 0.998 AC: 41488 AN: 41570

American (AMR) AF: 0.990 AC: 15152 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3358 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5152 AN: 5176

South Asian (SAS) AF: 0.983 AC: 4744 AN: 4826

European-Finnish (FIN) AF: 0.998 AC: 10599 AN: 10624

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67492 AN: 68048

Other (OTH) AF: 0.983 AC: 2078 AN: 2114

Alfa AF: 0.996 Hom.: 2402

Bravo AF: 0.993

Asia WGS AF: 0.988 AC: 3434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		0.096
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: rs2286103; hg19: chr7-38779675;