rs201251363

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-89711882-A-G
• chr16-89711882-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004913.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS9D1	NM_004913.3	MANE Select	c.747T>C	p.His249His	splice_region synonymous	Exon 8 of 15	NP_004904.2	Q9Y2B5-1
	VPS9D1-AS1	NR_036480.1		n.27A>G		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS9D1	ENST00000389386.8	TSL:1 MANE Select	c.747T>C	p.His249His	splice_region synonymous	Exon 8 of 15	ENSP00000374037.3	Q9Y2B5-1
	VPS9D1	ENST00000561976.5	TSL:1	c.537T>C	p.His179His	splice_region synonymous	Exon 7 of 14	ENSP00000454244.1	H3BM58
	VPS9D1	ENST00000563798.1	TSL:3	n.*256T>C		splice_region non_coding_transcript_exon	Exon 5 of 6	ENSP00000454889.1	H3BNK1

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

GnomAD2 exomes AF: 0.00111 AC: 170 AN: 153566 AF XY: 0.000785

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 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

African (AFR) AF: 0.0170 AC: 536 AN: 31598

American (AMR) AF: 0.00115 AC: 41 AN: 35720

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35756

South Asian (SAS) AF: 0.0000757 AC: 6 AN: 79244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48478

Middle Eastern (MID) AF: 0.000529 AC: 3 AN: 5672

European-Non Finnish (NFE) AF: 0.0000565 AC: 61 AN: 1078738

Other (OTH) AF: 0.00104 AC: 60 AN: 57960

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

African (AFR) AF: 0.0164 AC: 681 AN: 41528

American (AMR) AF: 0.00209 AC: 32 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67936

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00108 Hom.: 4

Bravo AF: 0.00541

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.8
DANN	Benign	0.47
PhyloP100		-1.7
Mutation Taster		=36/64	disease causing

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

Other links and lift over

dbSNP: rs201251363; hg19: chr16-89778290;