7-38742250-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014396.4(VPS41):c.2123-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0743 in 880,614 control chromosomes in the GnomAD database, including 2,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (419 hom., cov: 33)
  • Exomes 𝑓: 0.077 (2527 hom.)
• Consequence: VPS41 NM_014396.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.559

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 7-38742250-T-C is Benign according to our data. Variant chr7-38742250-T-C is described in ClinVar as [Benign]. Clinvar id is 1273716.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.2123-129A>G		intron_variant		ENST00000310301.9
VPS41	NM_080631.4	c.2048-129A>G		intron_variant
VPS41	XM_017011988.2	c.968-129A>G		intron_variant
VPS41	XR_007060008.1	n.2140-129A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.2123-129A>G		intron_variant		1	NM_014396.4	P1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9250 AN: 152170 Hom.: 420 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0479

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0771 AC: 56181 AN: 728326 Hom.: 2527 AF XY: 0.0794 AC XY: 29528 AN XY: 371772

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0349

Gnomad4 ASJ exome AF: 0.0734

Gnomad4 EAS exome AF: 0.000961

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.0902

Gnomad4 NFE exome AF: 0.0795

Gnomad4 OTH exome AF: 0.0750

GnomAD4 genome AF: 0.0608 AC: 9253 AN: 152288 Hom.: 419 Cov.: 33 AF XY: 0.0607 AC XY: 4519 AN XY: 74462

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.0878

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0814 Hom.: 94

Bravo AF: 0.0518

Asia WGS AF: 0.0590 AC: 205 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	13
Dann	Benign	0.87

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

Other links and lift over

dbSNP: rs36004953; hg19: chr7-38781850; COSMIC: COSV59651467;