10-51697910-C-T

Variant names:

• chr10-51697910-C-T
• rs201330739
• NM_015235.3:c.1640G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015235.3(CSTF2T):​c.1640G>A​(p.Gly547Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000663 in 150,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CSTF2T NM_015235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22003376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2T	NM_015235.3	c.1640G>A	p.Gly547Asp	missense_variant	Exon 1 of 1	ENST00000331173.6	NP_056050.1
PRKG1	NM_006258.4	c.593-106675C>T		intron_variant	Intron 3 of 17	ENST00000373980.11	NP_006249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTF2T	ENST00000331173.6	c.1640G>A	p.Gly547Asp	missense_variant	Exon 1 of 1	6	NM_015235.3	ENSP00000332444.4
PRKG1	ENST00000373980.11	c.593-106675C>T		intron_variant	Intron 3 of 17	1	NM_006258.4	ENSP00000363092.5

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150826 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150826 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73682

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.14	T
Polyphen		0.98	D
Vest4		0.29
MutPred		0.23		Loss of sheet (P = 0.0457);
MVP		0.41
MPC		0.29
ClinPred		0.87	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.43
gMVP		0.83

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: rs201330739; hg19: chr10-53457670;