rs974053

Positions:

• chr8-18695229-G-A
• chr8-18695229-G-C
• chr8-18695229-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015310.4(PSD3):​c.2173-39544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,188 control chromosomes in the GnomAD database, including 61,537 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 0.90 (61537 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD3	NM_015310.4	c.2173-39544C>T		intron_variant		ENST00000327040.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD3	ENST00000327040.13	c.2173-39544C>T		intron_variant		1	NM_015310.4	P3
PSD3	ENST00000286485.12	c.571-39544C>T		intron_variant		1		A1
PSD3	ENST00000523619.5	c.1978-39544C>T		intron_variant		1		A2
PSD3	ENST00000518315.5	c.*179-39544C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136161 AN: 152068 Hom.: 61521 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.895 AC: 136225 AN: 152188 Hom.: 61537 Cov.: 32 AF XY: 0.888 AC XY: 66099 AN XY: 74408

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.956

Gnomad4 OTH AF: 0.891

Alfa AF: 0.928 Hom.: 8189

Bravo AF: 0.879

Asia WGS AF: 0.784 AC: 2728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs974053; hg19: chr8-18552739;