rs28651847

Variant names:

• chr8-18556275-G-A
• rs28651847
• NM_015310.4:c.2862C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-18556275-G-A
• chr8-18556275-G-C
• chr8-18556275-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015310.4(PSD3):​c.2862C>T​(p.Pro954Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,613,814 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (54 hom.)
• Consequence: PSD3 NM_015310.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.50
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 8-18556275-G-A is Benign according to our data. Variant chr8-18556275-G-A is described in ClinVar as [Benign]. Clinvar id is 719443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2862C>T	p.Pro954Pro	synonymous_variant	Exon 15 of 16	ENST00000327040.13	NP_056125.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD3	ENST00000327040.13	c.2862C>T	p.Pro954Pro	synonymous_variant	Exon 15 of 16	1	NM_015310.4	ENSP00000324127.8

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2219 AN: 152028 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00393 AC: 986 AN: 251170 AF XY: 0.00287

Gnomad AFR exome AF: 0.0531

Gnomad AMR exome AF: 0.00223

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000969

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00148 AC: 2166 AN: 1461670 Hom.: 54 Cov.: 30 AF XY: 0.00128 AC XY: 932 AN XY: 727132

African (AFR) AF: 0.0522 AC: 1748 AN: 33476

American (AMR) AF: 0.00237 AC: 106 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000939 AC: 81 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1111860

Other (OTH) AF: 0.00280 AC: 169 AN: 60388

GnomAD4 genome AF: 0.0146 AC: 2224 AN: 152144 Hom.: 52 Cov.: 32 AF XY: 0.0140 AC XY: 1041 AN XY: 74376

African (AFR) AF: 0.0510 AC: 2116 AN: 41478

American (AMR) AF: 0.00523 AC: 80 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68006

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00655 Hom.: 12

Bravo AF: 0.0167

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.52
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism

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: rs28651847; hg19: chr8-18413785;