2-113206162-C-T

Position:

• chr2-113206162-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012455.3(PSD4):​c.*4747C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,122 control chromosomes in the GnomAD database, including 14,808 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 0.42 (14805 hom., cov: 33)
  • Exomes 𝑓: 0.38 (3 hom.)
• Consequence: PSD4 NM_012455.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522

Genes affected

PSD4 (HGNC:19096): (pleckstrin and Sec7 domain containing 4) 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. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PSD4	NM_012455.3	c.*4747C>T		3_prime_UTR_variant	17/17	ENST00000245796.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PSD4	ENST00000245796.11	c.*4747C>T		3_prime_UTR_variant	17/17	1	NM_012455.3	P3
PSD4	ENST00000441564.7	c.*4747C>T		3_prime_UTR_variant	17/17	1		A2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64444 AN: 151956 Hom.: 14813 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.468

GnomAD4 exome AF: 0.375 AC: 18 AN: 48 Hom.: 3 Cov.: 0 AF XY: 0.417 AC XY: 15 AN XY: 36

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.424 AC: 64446 AN: 152074 Hom.: 14805 Cov.: 33 AF XY: 0.427 AC XY: 31734 AN XY: 74328

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.468

Alfa AF: 0.465 Hom.: 7839

Bravo AF: 0.427

Asia WGS AF: 0.520 AC: 1811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12620738; hg19: chr2-113963739;