8-18921616-G-T

Variant names:

• chr8-18921616-G-T
• rs12155975
• NM_015310.4:c.130+14418C>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.130+14418C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,156 control chromosomes in the GnomAD database, including 2,330 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 0.16 (2330 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11
• Publications: 4 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 = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.130+14418C>A		intron_variant	Intron 2 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.130+14418C>A		intron_variant	Intron 2 of 15	1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25092 AN: 152038 Hom.: 2327 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.165 AC: 25100 AN: 152156 Hom.: 2330 Cov.: 32 AF XY: 0.169 AC XY: 12571 AN XY: 74384

African (AFR) AF: 0.147 AC: 6116 AN: 41508

American (AMR) AF: 0.250 AC: 3823 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1634 AN: 5170

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4820

European-Finnish (FIN) AF: 0.147 AC: 1561 AN: 10590

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9564 AN: 67998

Other (OTH) AF: 0.185 AC: 392 AN: 2114

Alfa AF: 0.150 Hom.: 2976

Bravo AF: 0.172

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.061
DANN	Benign	0.40
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: rs12155975; hg19: chr8-18779126;