chr17-28611166-C-G

Variant names:

• chr17-28611166-C-G
• rs1038058093
• NM_001174103.2:c.988G>C

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>C​(p.Gly330Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,060 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: RSKR NM_001174103.2 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.23690793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSKR	NM_001174103.2	c.988G>C	p.Gly330Arg	missense_variant	Exon 11 of 12	ENST00000301037.11	NP_001167574.1
SPAG5-AS1	NR_040012.1	n.273-5119C>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSKR	ENST00000301037.11	c.988G>C	p.Gly330Arg	missense_variant	Exon 11 of 12	5	NM_001174103.2	ENSP00000301037.5
ENSG00000258472	ENST00000531839.5	c.524+1865G>C		intron_variant	Intron 4 of 7	2		ENSP00000431165.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152060 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74258

Gnomad4 AFR AF: 0.0000242

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.83
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.73	T;.
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.71	T
PROVEAN	Benign	-1.2	.;N
REVEL	Benign	0.12
Sift	Benign	0.24	.;T
Sift4G	Benign	0.38	T;T
Vest4		0.27
MutPred		0.48		.;Loss of catalytic residue at S332 (P = 0.0632);
MVP		0.68
MPC		0.20
ClinPred		0.17	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.47

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;