rs1056890

chr10-102403013-G-Achr10-102403013-G-C

Variant summary

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

The NM_002779.5(PSD):c.*187C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 309,338 control chromosomes in the GnomAD database, including 19,644 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 0.31 (7011 hom., cov: 28)
  • Exomes 𝑓: 0.44 (12633 hom.)
• Consequence: PSD NM_002779.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD	NM_002779.5	c.*187C>T		3_prime_UTR_variant	17/17	ENST00000020673.6
PSD	NM_001270965.2	c.*187C>T		3_prime_UTR_variant	18/18
PSD	NM_001270966.2	c.*187C>T		3_prime_UTR_variant	18/18
PSD	NR_073110.2	n.1554C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD	ENST00000020673.6	c.*187C>T		3_prime_UTR_variant	17/17	1	NM_002779.5	P1
PSD	ENST00000406432.5	c.*187C>T		3_prime_UTR_variant	18/18	1		P1
PSD	ENST00000611678.4	c.*187C>T		3_prime_UTR_variant	18/18	1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 43820 AN: 140728 Hom.: 7011 Cov.: 28

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.441 AC: 74269 AN: 168544 Hom.: 12633 Cov.: 4 AF XY: 0.444 AC XY: 38279 AN XY: 86244

Gnomad4 AFR exome AF: 0.278

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.359

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.311 AC: 43818 AN: 140794 Hom.: 7011 Cov.: 28 AF XY: 0.319 AC XY: 21688 AN XY: 68086

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.342

Alfa AF: 0.339 Hom.: 11139

Bravo AF: 0.285

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.15
Dann	Benign	0.90

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: rs1056890; hg19: chr10-104162770;