10-102403990-C-T

Position:

• chr10-102403990-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002779.5(PSD):​c.2701-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,547,986 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (7 hom.)
• Consequence: PSD NM_002779.5 splice_region, intron
• Scores: Splicing: ADA: 0.0007850
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.851

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-102403990-C-T is Benign according to our data. Variant chr10-102403990-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 769787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSD	NM_002779.5	c.2701-5G>A		splice_region_variant, intron_variant		ENST00000020673.6	NP_002770.3
PSD	NM_001270965.2	c.2701-5G>A		splice_region_variant, intron_variant			NP_001257894.1
PSD	NM_001270966.2	c.1564-5G>A		splice_region_variant, intron_variant			NP_001257895.1
PSD	NR_073110.2	n.993-5G>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSD	ENST00000020673.6	c.2701-5G>A		splice_region_variant, intron_variant		1	NM_002779.5	ENSP00000020673.5
PSD	ENST00000406432.5	c.2701-5G>A		splice_region_variant, intron_variant		1		ENSP00000384830.1
PSD	ENST00000611678.4	c.1564-5G>A		splice_region_variant, intron_variant		1		ENSP00000481250.1

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000945 AC: 148 AN: 156678 Hom.: 1 AF XY: 0.000996 AC XY: 83 AN XY: 83354

Gnomad AFR exome AF: 0.000214

Gnomad AMR exome AF: 0.000396

Gnomad ASJ exome AF: 0.000355

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000393

Gnomad NFE exome AF: 0.00191

Gnomad OTH exome AF: 0.00156

GnomAD4 exome AF: 0.00208 AC: 2897 AN: 1395688 Hom.: 7 Cov.: 33 AF XY: 0.00201 AC XY: 1384 AN XY: 689132

Gnomad4 AFR exome AF: 0.000156

Gnomad4 AMR exome AF: 0.000549

Gnomad4 ASJ exome AF: 0.000159

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000501

Gnomad4 FIN exome AF: 0.000407

Gnomad4 NFE exome AF: 0.00253

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00111 AC: 169 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.000967 AC XY: 72 AN XY: 74482

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00203

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00153 Hom.: 0

Bravo AF: 0.000982

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.78
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00078
dbscSNV1_RF	Benign	0.098
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: rs181250655; hg19: chr10-104163747;