7-38726185-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.*61A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 1,172,904 control chromosomes in the GnomAD database, including 4,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.086 (635 hom., cov: 32)
  • Exomes 𝑓: 0.079 (3602 hom.)
• Consequence: VPS41 NM_014396.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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=-0.82).
• BP6: Variant 7-38726185-T-C is Benign according to our data. Variant chr7-38726185-T-C is described in ClinVar as [Benign]. Clinvar id is 1259616.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.*61A>G		3_prime_UTR_variant	29/29	ENST00000310301.9
VPS41	NM_080631.4	c.*61A>G		3_prime_UTR_variant	28/28
VPS41	XM_017011988.2	c.*61A>G		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.*61A>G		3_prime_UTR_variant	29/29	1	NM_014396.4	P1
VPS41	ENST00000395969.6	c.*61A>G		3_prime_UTR_variant	28/28	5
VPS41	ENST00000490924.1	n.420A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13075 AN: 152060 Hom.: 632 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0592

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0838

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0742

GnomAD4 exome AF: 0.0794 AC: 81083 AN: 1020726 Hom.: 3602 Cov.: 13 AF XY: 0.0818 AC XY: 43119 AN XY: 527152

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0336

Gnomad4 ASJ exome AF: 0.0823

Gnomad4 EAS exome AF: 0.00986

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0856

Gnomad4 NFE exome AF: 0.0784

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0861 AC: 13100 AN: 152178 Hom.: 635 Cov.: 32 AF XY: 0.0859 AC XY: 6394 AN XY: 74412

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0838

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0787 Hom.: 434

Bravo AF: 0.0808

Asia WGS AF: 0.0750 AC: 262 AN: 3478

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	-0.82
Cadd	Benign	0.41
Dann	Benign	0.72

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: rs13235997; hg19: chr7-38765785;