rs4921617

Variant names:

• chr8-18924537-C-T
• rs4921617
• NM_015310.4:c.130+11497G>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+11497G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,058 control chromosomes in the GnomAD database, including 17,321 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 0.46 (17321 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• Publications: 7 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.130+11497G>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+11497G>A		intron_variant	Intron 2 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000520789.1	n.746G>A		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70038 AN: 151940 Hom.: 17288 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.463

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.461 AC: 70125 AN: 152058 Hom.: 17321 Cov.: 32 AF XY: 0.463 AC XY: 34439 AN XY: 74316

African (AFR) AF: 0.619 AC: 25676 AN: 41468

American (AMR) AF: 0.526 AC: 8042 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1532 AN: 3466

East Asian (EAS) AF: 0.674 AC: 3491 AN: 5178

South Asian (SAS) AF: 0.482 AC: 2329 AN: 4828

European-Finnish (FIN) AF: 0.335 AC: 3536 AN: 10550

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24012 AN: 67972

Other (OTH) AF: 0.465 AC: 984 AN: 2114

Alfa AF: 0.407 Hom.: 25299

Bravo AF: 0.484

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.12
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: rs4921617; hg19: chr8-18782047;