rs7015570

Variant names:

• chr8-18662569-A-G
• rs7015570
• NM_015310.4:c.2173-6884T>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.2173-6884T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,132 control chromosomes in the GnomAD database, including 8,854 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 0.29 (8854 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 3 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: AD 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	NM_015310.4	MANE Select	c.2173-6884T>C		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.2557-6884T>C		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.2476-6884T>C		intron	N/A	NP_001399794.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	ENST00000327040.13	TSL:1 MANE Select	c.2173-6884T>C		intron	N/A	ENSP00000324127.8
	PSD3	ENST00000523619.5	TSL:1	c.1978-6884T>C		intron	N/A	ENSP00000430640.1
	PSD3	ENST00000286485.12	TSL:1	c.571-6884T>C		intron	N/A	ENSP00000286485.8

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43865 AN: 152014 Hom.: 8813 Cov.: 33

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.289 AC: 43961 AN: 152132 Hom.: 8854 Cov.: 33 AF XY: 0.296 AC XY: 22030 AN XY: 74384

African (AFR) AF: 0.514 AC: 21334 AN: 41470

American (AMR) AF: 0.309 AC: 4721 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3462

East Asian (EAS) AF: 0.662 AC: 3430 AN: 5178

South Asian (SAS) AF: 0.423 AC: 2040 AN: 4820

European-Finnish (FIN) AF: 0.141 AC: 1498 AN: 10602

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9805 AN: 67990

Other (OTH) AF: 0.258 AC: 546 AN: 2116

Alfa AF: 0.185 Hom.: 5423

Bravo AF: 0.309

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.4
DANN	Benign	0.62
PhyloP100		-0.013
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: rs7015570; hg19: chr8-18520079;