chr17-28611240-G-A

Variant names:

• chr17-28611240-G-A
• NM_001174103.2:c.914C>T

Variant summary

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

The NM_001174103.2(RSKR):​c.914C>T​(p.Ala305Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RSKR NM_001174103.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.00

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSKR	NM_001174103.2	c.914C>T	p.Ala305Val	missense_variant	Exon 11 of 12	ENST00000301037.11	NP_001167574.1
SPAG5-AS1	NR_040012.1	n.273-5045G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSKR	ENST00000301037.11	c.914C>T	p.Ala305Val	missense_variant	Exon 11 of 12	5	NM_001174103.2	ENSP00000301037.5
ENSG00000258472	ENST00000531839.5	c.524+1791C>T		intron_variant	Intron 4 of 7	2		ENSP00000431165.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.914C>T (p.A305V) alteration is located in exon 11 (coding exon 11) of the SGK494 gene. This alteration results from a C to T substitution at nucleotide position 914, causing the alanine (A) at amino acid position 305 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D;.
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-1.2	T
PROVEAN	Benign	-1.5	.;N
REVEL	Benign	0.17
Sift	Benign	0.17	.;T
Sift4G	Uncertain	0.057	T;T
Vest4		0.29
MutPred		0.60		.;Loss of ubiquitination at K300 (P = 0.141);
MVP		0.45
MPC		0.28
ClinPred		0.87	D
GERP RS		5.3
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-26938258;