rs11191283

Positions:

• chr10-102403812-G-A

Variant summary

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

The NM_002779.5(PSD):​c.2844+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,599,232 control chromosomes in the GnomAD database, including 90,025 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 0.27 (6657 hom., cov: 33)
  • Exomes 𝑓: 0.33 (83368 hom.)
• Consequence: PSD NM_002779.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822

Genes affected

PSD (HGNC:9507): (pleckstrin and Sec7 domain containing) This gene encodes a Plekstrin homology and SEC7 domains-containing protein that functions as a guanine nucleotide exchange factor. The encoded protein regulates signal transduction by activating ADP-ribosylation factor 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

PSD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5	c.2844+30C>T		intron_variant		ENST00000020673.6	NP_002770.3
PSD	NM_001270965.2	c.2844+30C>T		intron_variant			NP_001257894.1
PSD	NM_001270966.2	c.1707+30C>T		intron_variant			NP_001257895.1
PSD	NR_073110.2	n.1136+30C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD	ENST00000020673.6	c.2844+30C>T		intron_variant		1	NM_002779.5	ENSP00000020673.5
PSD	ENST00000406432.5	c.2844+30C>T		intron_variant		1		ENSP00000384830.1
PSD	ENST00000611678.4	c.1707+30C>T		intron_variant		1		ENSP00000481250.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41288 AN: 151964 Hom.: 6658 Cov.: 33

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.334 AC: 78901 AN: 236582 Hom.: 14080 AF XY: 0.343 AC XY: 43942 AN XY: 127936

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.190

Gnomad SAS exome AF: 0.451

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.342

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.334 AC: 482988 AN: 1447150 Hom.: 83368 Cov.: 34 AF XY: 0.338 AC XY: 242955 AN XY: 718180

Gnomad4 AFR exome AF: 0.0817

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.271 AC: 41284 AN: 152082 Hom.: 6657 Cov.: 33 AF XY: 0.275 AC XY: 20471 AN XY: 74340

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.309

Alfa AF: 0.295 Hom.: 1498

Bravo AF: 0.264

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.75

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: rs11191283; hg19: chr10-104163569; COSMIC: COSV50041699; COSMIC: COSV50041699;