17-28610608-A-G

Variant names:

• chr17-28610608-A-G
• rs771931562
• NM_001174103.2:c.1103T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001174103.2(RSKR):​c.1103T>C​(p.Leu368Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L368R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSKR NM_001174103.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174103.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSKR	NM_001174103.2	MANE Select	c.1103T>C	p.Leu368Pro	missense	Exon 12 of 12	NP_001167574.1	Q96LW2
	SPAG5-AS1	NR_040012.1		n.273-5677A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSKR	ENST00000301037.11	TSL:5 MANE Select	c.1103T>C	p.Leu368Pro	missense	Exon 12 of 12	ENSP00000301037.5
	ENSG00000258472	ENST00000531839.5	TSL:2	c.524+2423T>C		intron	N/A	ENSP00000431165.1	E9PMD0
	SPAG5-AS1	ENST00000414744.2	TSL:1	n.1051-5677A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-1.2	T
PhyloP100		6.0
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.033	D
Vest4		0.42
MutPred		0.64		Gain of disorder (P = 0.007)
MVP		0.51
MPC		0.60
ClinPred		0.94	D
GERP RS		5.5
gMVP		0.82

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

Other links and lift over

dbSNP: rs771931562; hg19: chr17-26937626;