chr8-18708295-A-G

Variant names:

• chr8-18708295-A-G
• rs901729
• NM_015310.4:c.2173-52610T>C

Variant summary

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

The NM_015310.4(PSD3):​c.2173-52610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,086 control chromosomes in the GnomAD database, including 46,762 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 0.75 (46762 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 2 publications found

Genes affected

PSD3 (HGNC:19093): (pleckstrin and Sec7 domain containing 3) Predicted to enable guanyl-nucleotide exchange factor activity and phospholipid binding activity. Predicted to be involved in regulation of ARF protein signal transduction and regulation of catalytic activity. Predicted to be located in membrane. Predicted to be active in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

PSD3 Gene-Disease associations (from GenCC):

• antecubital pterygium syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015310.4. 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
	PSD3	NM_015310.4	MANE Select	c.2173-52610T>C		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.2556+26940T>C		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.2476-52610T>C		intron	N/A	NP_001399794.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	ENST00000327040.13	TSL:1 MANE Select	c.2173-52610T>C		intron	N/A	ENSP00000324127.8	Q9NYI0-2
	PSD3	ENST00000523619.5	TSL:1	c.1978-52610T>C		intron	N/A	ENSP00000430640.1	E5RJ29
	PSD3	ENST00000286485.12	TSL:1	c.571-52610T>C		intron	N/A	ENSP00000286485.8	Q9NYI0-3

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113832 AN: 151968 Hom.: 46762 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.935

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.749 AC: 113846 AN: 152086 Hom.: 46762 Cov.: 32 AF XY: 0.745 AC XY: 55406 AN XY: 74366

African (AFR) AF: 0.408 AC: 16902 AN: 41424

American (AMR) AF: 0.721 AC: 11017 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.935 AC: 3246 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2700 AN: 5148

South Asian (SAS) AF: 0.760 AC: 3652 AN: 4808

European-Finnish (FIN) AF: 0.900 AC: 9554 AN: 10616

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 63996 AN: 68020

Other (OTH) AF: 0.780 AC: 1649 AN: 2114

Alfa AF: 0.877 Hom.: 95738

Bravo AF: 0.720

Asia WGS AF: 0.654 AC: 2273 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		0.086
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs901729; hg19: chr8-18565805;