1-213071052-T-A

Variant names:

• chr1-213071052-T-A
• rs763495217
• NM_012424.6:c.141+11T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012424.6(RPS6KC1):​c.141+11T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,344,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.4e-7 (0 hom.)
• Consequence: RPS6KC1 NM_012424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 publications found

Genes affected

RPS6KC1 (HGNC:10439): (ribosomal protein S6 kinase C1) Sphingosine kinase catalyzes the formation of sphingosine 1 phosphate, a lipid cellular messenger. The protein encoded by this gene can bind to sphingosine kinase and to phosphatidylinositol 3-phosphate, suggesting a role in sphingosine 1 phophate signaling. The encoded protein can also bind to peroxiredoxin-3 and may help transport it to mitochondria. [provided by RefSeq, Mar 2017]

RPS6KC1 Gene-Disease associations (from GenCC):

• periventricular leukomalacia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012424.6. 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
	RPS6KC1	NM_012424.6	MANE Select	c.141+11T>A		intron	N/A	NP_036556.2
	RPS6KC1	NM_001136138.4		c.106-6644T>A		intron	N/A	NP_001129610.1	Q96S38-2
	RPS6KC1	NM_001349646.2		c.141+11T>A		intron	N/A	NP_001336575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KC1	ENST00000366960.8	TSL:1 MANE Select	c.141+11T>A		intron	N/A	ENSP00000355927.3	Q96S38-1
	RPS6KC1	ENST00000543354.5	TSL:1	c.-282+11T>A		intron	N/A	ENSP00000439282.2	F6RJM5
	RPS6KC1	ENST00000614059.4	TSL:1	c.-481+11T>A		intron	N/A	ENSP00000483873.1	F5H7T0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1344392 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 672510

African (AFR) AF: 0.00 AC: 0 AN: 29122

American (AMR) AF: 0.00 AC: 0 AN: 34036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 37176

South Asian (SAS) AF: 0.00 AC: 0 AN: 75982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 9.71e-7 AC: 1 AN: 1029890

Other (OTH) AF: 0.00 AC: 0 AN: 55986

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.76
PhyloP100		2.0

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: rs763495217; hg19: chr1-213244394;