8-18871228-C-G

Variant names:

• chr8-18871228-C-G
• rs6998537
• NM_015310.4:c.1238+398G>C

Variant summary

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

The NM_015310.4(PSD3):​c.1238+398G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,122 control chromosomes in the GnomAD database, including 2,048 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 0.15 (2048 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.1238+398G>C		intron_variant	Intron 3 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.1238+398G>C		intron_variant	Intron 3 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000523619.5	c.1043+398G>C		intron_variant	Intron 2 of 14	1		ENSP00000430640.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23314 AN: 152004 Hom.: 2043 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.153 AC: 23342 AN: 152122 Hom.: 2048 Cov.: 32 AF XY: 0.158 AC XY: 11732 AN XY: 74340

African (AFR) AF: 0.221 AC: 9144 AN: 41466

American (AMR) AF: 0.153 AC: 2346 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 499 AN: 3468

East Asian (EAS) AF: 0.277 AC: 1436 AN: 5176

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4816

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7167 AN: 68000

Other (OTH) AF: 0.154 AC: 326 AN: 2116

Alfa AF: 0.132 Hom.: 181

Bravo AF: 0.155

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.39
PhyloP100		-0.66
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: rs6998537; hg19: chr8-18728738;