8-18729794-T-C

Variant names:

• chr8-18729794-T-C
• rs901732
• NM_015310.4:c.2172+35655A>G

Variant summary

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

The NM_015310.4(PSD3):​c.2172+35655A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,216 control chromosomes in the GnomAD database, including 67,550 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 0.94 (67550 hom., cov: 31)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• 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

ENSG00000187229 (HGNC:58211):

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 (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2172+35655A>G		intron_variant	Intron 9 of 15	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2172+35655A>G		intron_variant	Intron 9 of 15	1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143213 AN: 152098 Hom.: 67519 Cov.: 31

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.906

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.939

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

GnomAD4 genome AF: 0.941 AC: 143302 AN: 152216 Hom.: 67550 Cov.: 31 AF XY: 0.937 AC XY: 69750 AN XY: 74426

African (AFR) AF: 0.956 AC: 39718 AN: 41542

American (AMR) AF: 0.866 AC: 13223 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3205 AN: 3468

East Asian (EAS) AF: 0.825 AC: 4264 AN: 5166

South Asian (SAS) AF: 0.906 AC: 4367 AN: 4818

European-Finnish (FIN) AF: 0.964 AC: 10240 AN: 10622

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65154 AN: 68010

Other (OTH) AF: 0.940 AC: 1983 AN: 2110

Alfa AF: 0.955 Hom.: 8489

Bravo AF: 0.933

Asia WGS AF: 0.889 AC: 3090 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs901732; hg19: chr8-18587304;