rs6994627

chr8-19000729-G-Achr8-19000729-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.21+12834C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 151,720 control chromosomes in the GnomAD database, including 8,459 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 0.32 (8458 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD3	NM_015310.4	c.21+12834C>T		intron_variant		ENST00000327040.13
LOC105379303	XR_949546.3	n.339G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD3	ENST00000327040.13	c.21+12834C>T		intron_variant		1	NM_015310.4	P3
	ENST00000522670.1	n.322G>A		non_coding_transcript_exon_variant	3/3	4
PSD3	ENST00000521475.1	c.325-64587C>T		intron_variant		2
PSD3	ENST00000521841.1	n.401+13331C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48625 AN: 151596 Hom.: 8460 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.321 AC: 48640 AN: 151716 Hom.: 8458 Cov.: 32 AF XY: 0.319 AC XY: 23644 AN XY: 74148

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.312

Alfa AF: 0.343 Hom.: 11509

Bravo AF: 0.309

Asia WGS AF: 0.355 AC: 1233 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.4
Dann	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6994627; hg19: chr8-18858239;