chr16-89711882-A-G

Variant names:

• chr16-89711882-A-G
• rs201251363
• NM_004913.3:c.747T>C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_004913.3(VPS9D1):​c.747T>C​(p.His249His) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000923 in 1,550,402 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: VPS9D1 NM_004913.3 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

Genes affected

VPS9D1 (HGNC:13526): (VPS9 domain containing 1) Enables identical protein binding activity. Predicted to be involved in ATP synthesis coupled proton transport. [provided by Alliance of Genome Resources, Apr 2022]

VPS9D1-AS1 (HGNC:48915): (VPS9D1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 16-89711882-A-G is Benign according to our data. Variant chr16-89711882-A-G is described in ClinVar as [Benign]. Clinvar id is 715687.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00475 (723/152078) while in subpopulation AFR AF= 0.0164 (681/41528). AF 95% confidence interval is 0.0154. There are 4 homozygotes in gnomad4. There are 349 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS9D1	NM_004913.3	c.747T>C	p.His249His	splice_region_variant, synonymous_variant	Exon 8 of 15	ENST00000389386.8	NP_004904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS9D1	ENST00000389386.8	c.747T>C	p.His249His	splice_region_variant, synonymous_variant	Exon 8 of 15	1	NM_004913.3	ENSP00000374037.3
VPS9D1	ENST00000561976.5	c.537T>C	p.His179His	splice_region_variant, synonymous_variant	Exon 7 of 14	1		ENSP00000454244.1
VPS9D1	ENST00000563798.1	n.*256T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 6	3		ENSP00000454889.1
VPS9D1	ENST00000563798.1	n.*256T>C		3_prime_UTR_variant	Exon 5 of 6	3		ENSP00000454889.1

Frequencies

GnomAD3 genomes AF: 0.00476 AC: 724 AN: 151962 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00111 AC: 170 AN: 153566 Hom.: 0 AF XY: 0.000785 AC XY: 64 AN XY: 81498

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.000118

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000845

Gnomad OTH exome AF: 0.000231

GnomAD4 exome AF: 0.000506 AC: 708 AN: 1398324 Hom.: 3 Cov.: 32 AF XY: 0.000445 AC XY: 307 AN XY: 689704

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.00115

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000757

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000565

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00475 AC: 723 AN: 152078 Hom.: 4 Cov.: 33 AF XY: 0.00469 AC XY: 349 AN XY: 74362

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000835 Hom.: 3

Bravo AF: 0.00541

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.8
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs201251363; hg19: chr16-89778290;