rs599839

Positions:

• chr1-109279544-G-A
• chr1-109279544-G-C
• chr1-109279544-G-T

Variant summary

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

The 1-109279544-G-A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,288 control chromosomes in the GnomAD database, including 35,004 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 0.64 (34921 hom., cov: 32)
  • Exomes 𝑓: 0.81 (83 hom.)
• Consequence: PSRC1 NM_001032291.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902

Genes affected

PSRC1 (HGNC:24472): (proline and serine rich coiled-coil 1) This gene encodes a proline-rich protein that is a target for regulation by the tumor suppressor protein p53. The encoded protein plays an important role in mitosis by recruiting and regulating microtubule depolymerases that destabalize microtubules. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PSRC1	NM_001032291.3			downstream_gene_variant		ENST00000369909.7	NP_001027462.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PSRC1	ENST00000369909.7			downstream_gene_variant		1	NM_001032291.3	ENSP00000358925	P2

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96922 AN: 151912 Hom.: 34921 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.685

GnomAD4 exome AF: 0.810 AC: 209 AN: 258 Hom.: 83 Cov.: 0 AF XY: 0.808 AC XY: 118 AN XY: 146

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.809

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.638 AC: 96942 AN: 152030 Hom.: 34921 Cov.: 32 AF XY: 0.641 AC XY: 47669 AN XY: 74326

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.775

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.688

Alfa AF: 0.754 Hom.: 60561

Bravo AF: 0.618

Asia WGS AF: 0.790 AC: 2749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs599839; hg19: chr1-109822166;