rs61736650

Variant names:

• chr11-64361956-C-G
• NM_003942.3:c.860C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-64361956-C-G
• chr11-64361956-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_003942.3(RPS6KA4):​c.860C>G​(p.Ala287Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000034 (0 hom.)
• Consequence: RPS6KA4 NM_003942.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30

Genes affected

RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18599671).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KA4	NM_003942.3	c.860C>G	p.Ala287Gly	missense_variant	Exon 8 of 17	ENST00000334205.9	NP_003933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KA4	ENST00000334205.9	c.860C>G	p.Ala287Gly	missense_variant	Exon 8 of 17	1	NM_003942.3	ENSP00000333896.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458238 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725652

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	.;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.38	.;N;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	1.0	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.61	T;T;T
Polyphen		0.012	B;B;.
Vest4		0.36
MutPred		0.47		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;
MVP		0.46
MPC		0.42
ClinPred		0.43	T
GERP RS		4.0
Varity_R		0.090
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr11-64129428;