14-74911482-G-C

Variant names:

• chr14-74911482-G-C
• rs3213716
• NM_031464.5:c.532-102C>G

Variant summary

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

The NM_031464.5(RPS6KL1):​c.532-102C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
• Consequence: RPS6KL1 NM_031464.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 12 publications found

Genes affected

RPS6KL1 (HGNC:20222): (ribosomal protein S6 kinase like 1) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in ribosome. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031464.5. 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
	RPS6KL1	NM_031464.5	MANE Select	c.532-102C>G		intron	N/A	NP_113652.2	Q9Y6S9-1
	RPS6KL1	NM_001370252.1		c.532-102C>G		intron	N/A	NP_001357181.1
	RPS6KL1	NM_001370253.1		c.487-102C>G		intron	N/A	NP_001357182.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KL1	ENST00000557413.6	TSL:5 MANE Select	c.532-102C>G		intron	N/A	ENSP00000450567.1	Q9Y6S9-1
	RPS6KL1	ENST00000555009.5	TSL:1	n.439-102C>G		intron	N/A	ENSP00000450660.1	Q9Y6S9-2
	RPS6KL1	ENST00000961459.1		c.580-102C>G		intron	N/A	ENSP00000631518.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.67
PhyloP100		-0.71
PromoterAI		-0.067	Neutral

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: rs3213716; hg19: chr14-75378185;