8-18816221-T-G

Variant names:

• chr8-18816221-T-G
• rs2638663
• NM_015310.4:c.1635-11323A>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.1635-11323A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,070 control chromosomes in the GnomAD database, including 22,572 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 (22572 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.1635-11323A>C		intron_variant	Intron 4 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.1635-11323A>C		intron_variant	Intron 4 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000523619.5	c.1440-11323A>C		intron_variant	Intron 3 of 14	1		ENSP00000430640.1
PSD3	ENST00000519851.5	c.-43-11323A>C		intron_variant	Intron 1 of 5	5		ENSP00000429069.1
PSD3	ENST00000518303.5	n.240-11323A>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81539 AN: 151952 Hom.: 22527 Cov.: 33

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.537 AC: 81636 AN: 152070 Hom.: 22572 Cov.: 33 AF XY: 0.536 AC XY: 39866 AN XY: 74314

African (AFR) AF: 0.609 AC: 25257 AN: 41454

American (AMR) AF: 0.432 AC: 6606 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1685 AN: 3472

East Asian (EAS) AF: 0.889 AC: 4594 AN: 5168

South Asian (SAS) AF: 0.591 AC: 2845 AN: 4816

European-Finnish (FIN) AF: 0.434 AC: 4584 AN: 10562

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34350 AN: 67994

Other (OTH) AF: 0.526 AC: 1112 AN: 2114

Alfa AF: 0.526 Hom.: 21112

Bravo AF: 0.538

Asia WGS AF: 0.717 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.42
PhyloP100		-1.7
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: rs2638663; hg19: chr8-18673731;