rs11601

chr10-51697364-G-Achr10-51697364-G-C

Variant summary

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

The NM_015235.3(CSTF2T):c.*335C>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 0.333 in 222,910 control chromosomes in the GnomAD database, including 16,251 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 0.37 (13474 hom., cov: 32)
  • Exomes 𝑓: 0.26 (2777 hom.)
• Consequence: CSTF2T NM_015235.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

Genes affected

CSTF2T (HGNC:17086): (cleavage stimulation factor subunit 2 tau variant) Enables RNA binding activity. Predicted to be involved in pre-mRNA cleavage required for polyadenylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PRKG1 (HGNC:9414): (protein kinase cGMP-dependent 1) Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSTF2T	NM_015235.3	c.*335C>T		3_prime_UTR_variant	1/1	ENST00000331173.6
PRKG1	NM_006258.4	c.593-107221G>A		intron_variant		ENST00000373980.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSTF2T	ENST00000331173.6	c.*335C>T		3_prime_UTR_variant	1/1		NM_015235.3	P1
PRKG1	ENST00000373980.11	c.593-107221G>A		intron_variant		1	NM_006258.4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55894 AN: 151786 Hom.: 13422 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.256 AC: 18187 AN: 71006 Hom.: 2777 Cov.: 0 AF XY: 0.257 AC XY: 9442 AN XY: 36736

Gnomad4 AFR exome AF: 0.700

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.369 AC: 56015 AN: 151904 Hom.: 13474 Cov.: 32 AF XY: 0.366 AC XY: 27148 AN XY: 74218

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.327

Alfa AF: 0.225 Hom.: 1391

Bravo AF: 0.392

Asia WGS AF: 0.344 AC: 1195 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.6
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs11601; hg19: chr10-53457124;