NM_015310.4:c.1238+1187T>C

Variant names:

• chr8-18870439-A-G
• rs3758141
• NM_015310.4:c.1238+1187T>C

Variant summary

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

The NM_015310.4(PSD3):​c.1238+1187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,992 control chromosomes in the GnomAD database, including 3,833 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 0.22 (3833 hom., cov: 31)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 6 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.1238+1187T>C		intron_variant	Intron 3 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.1238+1187T>C		intron_variant	Intron 3 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000523619.5	c.1043+1187T>C		intron_variant	Intron 2 of 14	1		ENSP00000430640.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32927 AN: 151874 Hom.: 3825 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.217 AC: 32968 AN: 151992 Hom.: 3833 Cov.: 31 AF XY: 0.220 AC XY: 16373 AN XY: 74288

African (AFR) AF: 0.296 AC: 12256 AN: 41432

American (AMR) AF: 0.243 AC: 3714 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 760 AN: 3472

East Asian (EAS) AF: 0.282 AC: 1446 AN: 5130

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4818

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10564

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.165 AC: 11188 AN: 67982

Other (OTH) AF: 0.212 AC: 446 AN: 2108

Alfa AF: 0.135 Hom.: 326

Bravo AF: 0.223

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		0.61
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: rs3758141; hg19: chr8-18727949;