16-89720447-C-T

Variant names:

• chr16-89720447-C-T
• rs3809646
• NM_004913.3:c.99+316G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004913.3(VPS9D1):​c.99+316G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,060,580 control chromosomes in the GnomAD database, including 207,618 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38769 hom., cov: 34)
  • Exomes 𝑓: 0.61 (168849 hom.)
• Consequence: VPS9D1 NM_004913.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 22 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]

ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

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.99+316G>A		intron	N/A	NP_004904.2
	ZNF276	NR_110128.2		n.80C>T		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS9D1	ENST00000389386.8	TSL:1 MANE Select	c.99+316G>A		intron	N/A	ENSP00000374037.3
	VPS9D1	ENST00000563798.1	TSL:3	n.99+316G>A		intron	N/A	ENSP00000454889.1
	VPS9D1	ENST00000906741.1		c.99+316G>A		intron	N/A	ENSP00000576800.1

Frequencies

GnomAD3 genomes AF: 0.697 AC: 106043 AN: 152112 Hom.: 38704 Cov.: 34

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.606 AC: 550218 AN: 908350 Hom.: 168849 Cov.: 31 AF XY: 0.606 AC XY: 256113 AN XY: 422676

African (AFR) AF: 0.900 AC: 16281 AN: 18092

American (AMR) AF: 0.694 AC: 2045 AN: 2946

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 4297 AN: 8166

East Asian (EAS) AF: 0.976 AC: 9635 AN: 9868

South Asian (SAS) AF: 0.788 AC: 13707 AN: 17404

European-Finnish (FIN) AF: 0.674 AC: 4100 AN: 6086

Middle Eastern (MID) AF: 0.613 AC: 1262 AN: 2058

European-Non Finnish (NFE) AF: 0.590 AC: 478492 AN: 811208

Other (OTH) AF: 0.627 AC: 20399 AN: 32522

GnomAD4 genome AF: 0.697 AC: 106171 AN: 152230 Hom.: 38769 Cov.: 34 AF XY: 0.706 AC XY: 52531 AN XY: 74430

African (AFR) AF: 0.886 AC: 36802 AN: 41554

American (AMR) AF: 0.661 AC: 10106 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3470

East Asian (EAS) AF: 0.984 AC: 5103 AN: 5188

South Asian (SAS) AF: 0.804 AC: 3883 AN: 4832

European-Finnish (FIN) AF: 0.692 AC: 7328 AN: 10588

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39175 AN: 67992

Other (OTH) AF: 0.644 AC: 1361 AN: 2114

Alfa AF: 0.620 Hom.: 67110

Bravo AF: 0.705

Asia WGS AF: 0.899 AC: 3125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-0.70
PromoterAI		0.040	Neutral
Mutation Taster		=289/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3809646; hg19: chr16-89786855;