rs974053

Variant names:

• chr8-18695229-G-A
• rs974053
• NM_015310.4:c.2173-39544C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-18695229-G-A
• chr8-18695229-G-C
• chr8-18695229-G-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.2173-39544C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,188 control chromosomes in the GnomAD database, including 61,537 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 0.90 (61537 hom., cov: 32)
• Consequence: PSD3 NM_015310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PSD3	NM_015310.4	c.2173-39544C>T		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.2173-39544C>T		intron_variant	Intron 9 of 15	1	NM_015310.4	ENSP00000324127.8
PSD3	ENST00000523619.5	c.1978-39544C>T		intron_variant	Intron 8 of 14	1		ENSP00000430640.1
PSD3	ENST00000286485.12	c.571-39544C>T		intron_variant	Intron 6 of 12	1		ENSP00000286485.8
PSD3	ENST00000518315.5	n.*179-39544C>T		intron_variant	Intron 7 of 13	2		ENSP00000428889.1

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136161 AN: 152068 Hom.: 61521 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.890

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

GnomAD4 genome AF: 0.895 AC: 136225 AN: 152188 Hom.: 61537 Cov.: 32 AF XY: 0.888 AC XY: 66099 AN XY: 74408

African (AFR) AF: 0.866 AC: 35946 AN: 41504

American (AMR) AF: 0.758 AC: 11591 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3231 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3271 AN: 5156

South Asian (SAS) AF: 0.886 AC: 4271 AN: 4822

European-Finnish (FIN) AF: 0.930 AC: 9859 AN: 10600

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

European-Non Finnish (NFE) AF: 0.956 AC: 65001 AN: 68020

Other (OTH) AF: 0.891 AC: 1886 AN: 2116

Alfa AF: 0.928 Hom.: 8189

Bravo AF: 0.879

Asia WGS AF: 0.784 AC: 2728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		0.029
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: rs974053; hg19: chr8-18552739;