8-18972204-C-T

Variant names:

• chr8-18972204-C-T
• rs6586789
• NM_015310.4:c.22-36062G>A

Variant summary

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

The NM_015310.4(PSD3):​c.22-36062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,028 control chromosomes in the GnomAD database, including 39,822 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 0.72 (39822 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.22-36062G>A		intron_variant	Intron 1 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.22-36062G>A		intron_variant	Intron 1 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000521475.1	c.325-36062G>A		intron_variant	Intron 1 of 1	2		ENSP00000428405.1
PSD3	ENST00000521841.1	n.402-36066G>A		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109437 AN: 151910 Hom.: 39813 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.716

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

GnomAD4 genome AF: 0.720 AC: 109490 AN: 152028 Hom.: 39822 Cov.: 32 AF XY: 0.719 AC XY: 53441 AN XY: 74280

African (AFR) AF: 0.631 AC: 26167 AN: 41454

American (AMR) AF: 0.728 AC: 11137 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 2756 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3279 AN: 5164

South Asian (SAS) AF: 0.768 AC: 3694 AN: 4810

European-Finnish (FIN) AF: 0.729 AC: 7696 AN: 10552

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52255 AN: 67968

Other (OTH) AF: 0.711 AC: 1499 AN: 2108

Alfa AF: 0.757 Hom.: 50159

Bravo AF: 0.714

Asia WGS AF: 0.692 AC: 2406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.45
PhyloP100		1.2
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: rs6586789; hg19: chr8-18829714;