NM_015310.4:c.130+14707A>G

Variant names:

• chr8-18921327-T-C
• rs1038848
• NM_015310.4:c.130+14707A>G

Variant summary

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

The NM_015310.4(PSD3):​c.130+14707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,076 control chromosomes in the GnomAD database, including 23,349 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 0.54 (23349 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 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.130+14707A>G		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.433+14707A>G		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.433+14707A>G		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.130+14707A>G		intron	N/A	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82243 AN: 151958 Hom.: 23350 Cov.: 33

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.541 AC: 82267 AN: 152076 Hom.: 23349 Cov.: 33 AF XY: 0.548 AC XY: 40753 AN XY: 74330

African (AFR) AF: 0.360 AC: 14931 AN: 41476

American (AMR) AF: 0.543 AC: 8295 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2069 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3570 AN: 5160

South Asian (SAS) AF: 0.592 AC: 2851 AN: 4812

European-Finnish (FIN) AF: 0.712 AC: 7541 AN: 10584

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41140 AN: 67972

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.581 Hom.: 49762

Bravo AF: 0.520

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.35
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1038848; hg19: chr8-18778837;