17-28611166-C-T

Position:

• chr17-28611166-C-T

Variant summary

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

The NM_001174103.2(RSKR):​c.988G>A​(p.Gly330Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RSKR NM_001174103.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48

Genes affected

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258472 (HGNC:):

SPAG5-AS1 (HGNC:41140): (SPAG5 antisense RNA 1)

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=0.22391167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSKR	NM_001174103.2	c.988G>A	p.Gly330Ser	missense_variant	11/12	ENST00000301037.11	NP_001167574.1
SPAG5-AS1	NR_040012.1	n.273-5119C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSKR	ENST00000301037.11	c.988G>A	p.Gly330Ser	missense_variant	11/12	5	NM_001174103.2	ENSP00000301037.5
ENSG00000258472	ENST00000531839.5	c.524+1865G>A		intron_variant		2		ENSP00000431165.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383990 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 682928

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.988G>A (p.G330S) alteration is located in exon 11 (coding exon 11) of the SGK494 gene. This alteration results from a G to A substitution at nucleotide position 988, causing the glycine (G) at amino acid position 330 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.85
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.66	T;.
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.74	T
PROVEAN	Benign	-0.40	.;N
REVEL	Benign	0.098
Sift	Benign	0.52	.;T
Sift4G	Benign	0.53	T;T
Vest4		0.15
MutPred		0.44		.;Gain of disorder (P = 0.0408);
MVP		0.71
MPC		0.091
ClinPred		0.16	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.30

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: rs1038058093; hg19: chr17-26938184;