17-28611163-G-A

Variant names:

• chr17-28611163-G-A
• rs907133005
• NM_001174103.2:c.991C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001174103.2(RSKR):​c.991C>T​(p.Leu331Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000723 in 1,383,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RSKR NM_001174103.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.07

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39272636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSKR	NM_001174103.2	c.991C>T	p.Leu331Phe	missense_variant	Exon 11 of 12	ENST00000301037.11	NP_001167574.1
SPAG5-AS1	NR_040012.1	n.273-5122G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSKR	ENST00000301037.11	c.991C>T	p.Leu331Phe	missense_variant	Exon 11 of 12	5	NM_001174103.2	ENSP00000301037.5
ENSG00000258472	ENST00000531839.5	c.524+1868C>T		intron_variant	Intron 4 of 7	2		ENSP00000431165.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000726 AC: 1 AN: 137656 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74478

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000445

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383964 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 682904

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.87
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.57	T;.
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Uncertain	-0.047	T
PROVEAN	Benign	-1.4	.;N
REVEL	Benign	0.19
Sift	Benign	0.27	.;T
Sift4G	Benign	0.18	T;T
Vest4		0.30
MutPred		0.74		.;Loss of disorder (P = 0.1446);
MVP		0.78
MPC		0.14
ClinPred		0.23	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs907133005; hg19: chr17-26938181;