7-38726125-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014396.4(VPS41):c.*121A>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 0.0154 in 680,930 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (53 hom., cov: 33)
  • Exomes 𝑓: 0.013 (84 hom.)
• Consequence: VPS41 NM_014396.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.437

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=-0.84).
• BP6: Variant 7-38726125-T-C is Benign according to our data. Variant chr7-38726125-T-C is described in ClinVar as [Benign]. Clinvar id is 1285662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0231 (3510/152228) while in subpopulation AFR AF= 0.0485 (2016/41546). AF 95% confidence interval is 0.0468. There are 53 homozygotes in gnomad4. There are 1630 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS41	NM_014396.4	c.*121A>G		3_prime_UTR_variant	29/29	ENST00000310301.9
VPS41	NM_080631.4	c.*121A>G		3_prime_UTR_variant	28/28
VPS41	XM_017011988.2	c.*121A>G		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS41	ENST00000310301.9	c.*121A>G		3_prime_UTR_variant	29/29	1	NM_014396.4	P1
VPS41	ENST00000395969.6	c.*121A>G		3_prime_UTR_variant	28/28	5
VPS41	ENST00000490924.1	n.480A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3508 AN: 152110 Hom.: 53 Cov.: 33

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00976

Gnomad FIN AF: 0.00727

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.0131 AC: 6948 AN: 528702 Hom.: 84 Cov.: 7 AF XY: 0.0125 AC XY: 3512 AN XY: 280080

Gnomad4 AFR exome AF: 0.0506

Gnomad4 AMR exome AF: 0.00974

Gnomad4 ASJ exome AF: 0.00170

Gnomad4 EAS exome AF: 0.000285

Gnomad4 SAS exome AF: 0.00798

Gnomad4 FIN exome AF: 0.00901

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0151

GnomAD4 genome AF: 0.0231 AC: 3510 AN: 152228 Hom.: 53 Cov.: 33 AF XY: 0.0219 AC XY: 1630 AN XY: 74434

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00956

Gnomad4 FIN AF: 0.00727

Gnomad4 NFE AF: 0.0152

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0186 Hom.: 3

Bravo AF: 0.0247

Asia WGS AF: 0.00751 AC: 27 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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.80
Dann	Benign	0.62

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: rs112468126; hg19: chr7-38765725;