chr8-18614350-A-C

Position:

• chr8-18614350-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124901896 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2411-13916T>G		intron_variant		ENST00000327040.13	NP_056125.3
LOC124901896	XR_007060838.1	n.18259T>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2411-13916T>G		intron_variant		1	NM_015310.4	ENSP00000324127	P3

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

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.637

Alfa AF: 0.634 Hom.: 34706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.45

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: rs13273158; hg19: chr8-18471860;