chr8-18614350-A-C

Variant names:

• chr8-18614350-A-C
• rs13273158
• NM_015310.4:c.2411-13916T>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.2411-13916T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 133,288 control chromosomes in the GnomAD database, including 24,334 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 0.62 (24334 hom., cov: 21)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 3 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

LOC124901896 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.65 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.2411-13916T>G		intron	N/A	NP_056125.3
	PSD3	NM_001412866.1		c.2795-13916T>G		intron	N/A	NP_001399795.1
	PSD3	NM_001412865.1		c.2714-13916T>G		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.2411-13916T>G		intron	N/A	ENSP00000324127.8
	PSD3	ENST00000523619.5	TSL:1	c.2216-13916T>G		intron	N/A	ENSP00000430640.1
	PSD3	ENST00000286485.12	TSL:1	c.809-13916T>G		intron	N/A	ENSP00000286485.8

Frequencies

GnomAD3 genomes AF: 0.618 AC: 82295 AN: 133196 Hom.: 24320 Cov.: 21

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.800

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.618 AC: 82335 AN: 133288 Hom.: 24334 Cov.: 21 AF XY: 0.611 AC XY: 38987 AN XY: 63764

African (AFR) AF: 0.601 AC: 20822 AN: 34666

American (AMR) AF: 0.571 AC: 7257 AN: 12702

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2335 AN: 3304

East Asian (EAS) AF: 0.453 AC: 1884 AN: 4160

South Asian (SAS) AF: 0.602 AC: 2514 AN: 4178

European-Finnish (FIN) AF: 0.505 AC: 3646 AN: 7226

Middle Eastern (MID) AF: 0.800 AC: 208 AN: 260

European-Non Finnish (NFE) AF: 0.655 AC: 41954 AN: 64068

Other (OTH) AF: 0.637 AC: 1192 AN: 1872

Alfa AF: 0.633 Hom.: 40287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-1.2
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: rs13273158; hg19: chr8-18471860;