8-18814273-A-C

Variant names:

• chr8-18814273-A-C
• rs2632841
• NM_015310.4:c.1635-9375T>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.1635-9375T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 152,098 control chromosomes in the GnomAD database, including 19,731 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 0.47 (19731 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• 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: Unknown 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	NM_015310.4	MANE Select	c.1635-9375T>G		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.1938-9375T>G		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.1938-9375T>G		intron	N/A	NP_001399794.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSD3	ENST00000327040.13	TSL:1 MANE Select	c.1635-9375T>G		intron	N/A	ENSP00000324127.8	Q9NYI0-2
	PSD3	ENST00000523619.5	TSL:1	c.1440-9375T>G		intron	N/A	ENSP00000430640.1	E5RJ29
	PSD3	ENST00000519851.5	TSL:5	c.-43-9375T>G		intron	N/A	ENSP00000429069.1	E5RJE4

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71988 AN: 151982 Hom.: 19721 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.473 AC: 72011 AN: 152098 Hom.: 19731 Cov.: 32 AF XY: 0.480 AC XY: 35671 AN XY: 74364

African (AFR) AF: 0.177 AC: 7357 AN: 41504

American (AMR) AF: 0.545 AC: 8335 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2066 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4098 AN: 5162

South Asian (SAS) AF: 0.540 AC: 2592 AN: 4802

European-Finnish (FIN) AF: 0.634 AC: 6708 AN: 10580

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39027 AN: 67976

Other (OTH) AF: 0.494 AC: 1045 AN: 2114

Alfa AF: 0.541 Hom.: 41766

Bravo AF: 0.457

Asia WGS AF: 0.635 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		0.27
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: rs2632841; hg19: chr8-18671783;