8-18668374-G-A

Variant names:

• chr8-18668374-G-A
• rs17695641
• NM_015310.4:c.2173-12689C>T

Variant summary

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

The NM_015310.4(PSD3):​c.2173-12689C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,298 control chromosomes in the GnomAD database, including 184 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 0.039 (184 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0982 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.2173-12689C>T		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.2557-12689C>T		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.2476-12689C>T		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.2173-12689C>T		intron	N/A	ENSP00000324127.8
	PSD3	ENST00000523619.5	TSL:1	c.1978-12689C>T		intron	N/A	ENSP00000430640.1
	PSD3	ENST00000286485.12	TSL:1	c.571-12689C>T		intron	N/A	ENSP00000286485.8

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5988 AN: 152180 Hom.: 182 Cov.: 33

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0630

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0395 AC: 6014 AN: 152298 Hom.: 184 Cov.: 33 AF XY: 0.0420 AC XY: 3131 AN XY: 74468

African (AFR) AF: 0.0516 AC: 2145 AN: 41550

American (AMR) AF: 0.102 AC: 1568 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3466

East Asian (EAS) AF: 0.0607 AC: 315 AN: 5186

South Asian (SAS) AF: 0.0635 AC: 306 AN: 4820

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0188 AC: 1282 AN: 68034

Other (OTH) AF: 0.0374 AC: 79 AN: 2112

Alfa AF: 0.0294 Hom.: 170

Bravo AF: 0.0446

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		0.21
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: rs17695641; hg19: chr8-18525884;