chr2-113206162-C-T

Variant names:

• chr2-113206162-C-T
• rs12620738
• NM_012455.3:c.*4747C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PSD4	NM_012455.3	c.*4747C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000245796.11	NP_036587.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PSD4	ENST00000245796.11	c.*4747C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_012455.3	ENSP00000245796.6
PSD4	ENST00000441564.7	c.*4747C>T		3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000413997.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 3 AN: 18

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.458 AC: 11 AN: 24

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.246 AC: 10192 AN: 41506

American (AMR) AF: 0.523 AC: 7993 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3470

East Asian (EAS) AF: 0.648 AC: 3346 AN: 5160

South Asian (SAS) AF: 0.505 AC: 2439 AN: 4826

European-Finnish (FIN) AF: 0.401 AC: 4236 AN: 10562

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32727 AN: 67954

Other (OTH) AF: 0.468 AC: 988 AN: 2112

Alfa AF: 0.464 Hom.: 8757

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
PhyloP100		0.52
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: rs12620738; hg19: chr2-113963739;