rs10503640

Variant names:

• chr8-18881817-A-G
• rs10503640
• NM_015310.4:c.131-9084T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-18881817-A-G
• chr8-18881817-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015310.4(PSD3):​c.131-9084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,190 control chromosomes in the GnomAD database, including 2,261 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 0.17 (2261 hom., cov: 33)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 3 publications found

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]

PSD3 Gene-Disease associations (from GenCC):

• antecubital pterygium syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.131-9084T>C		intron_variant	Intron 2 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.131-9084T>C		intron_variant	Intron 2 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000523619.5	c.-66+5119T>C		intron_variant	Intron 1 of 14	1		ENSP00000430640.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26302 AN: 152072 Hom.: 2260 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.173 AC: 26314 AN: 152190 Hom.: 2261 Cov.: 33 AF XY: 0.175 AC XY: 13044 AN XY: 74402

African (AFR) AF: 0.172 AC: 7127 AN: 41528

American (AMR) AF: 0.194 AC: 2966 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3472

East Asian (EAS) AF: 0.165 AC: 856 AN: 5182

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4816

European-Finnish (FIN) AF: 0.145 AC: 1540 AN: 10600

Middle Eastern (MID) AF: 0.193 AC: 56 AN: 290

European-Non Finnish (NFE) AF: 0.164 AC: 11181 AN: 67986

Other (OTH) AF: 0.170 AC: 359 AN: 2108

Alfa AF: 0.144 Hom.: 581

Bravo AF: 0.175

Asia WGS AF: 0.239 AC: 830 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.54
PhyloP100		-0.092
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10503640; hg19: chr8-18739327;