4-1699590-G-C

Variant names:

• chr4-1699590-G-C
• rs2247341
• NM_006527.4:c.453C>G

Variant summary

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

The NM_006527.4(SLBP):​c.453C>G​(p.Tyr151*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLBP NM_006527.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 0 publications found

Genes affected

SLBP (HGNC:10904): (stem-loop histone mRNA binding protein) This gene encodes a protein that binds to the stem-loop structure in replication-dependent histone mRNAs. Histone mRNAs do not contain introns or polyadenylation signals, and are processed by endonucleolytic cleavage. The stem-loop structure is essential for efficient processing but this structure also controls the transport, translation and stability of histone mRNAs. Expression of the protein is regulated during the cell cycle, increasing more than 10-fold during the latter part of G1. [provided by RefSeq, Jul 2008]

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_006527.4. 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
	SLBP	NM_006527.4	MANE Select	c.453C>G	p.Tyr151*	stop_gained	Exon 5 of 8	NP_006518.1	Q14493-1
	SLBP	NM_001306074.2		c.348C>G	p.Tyr116*	stop_gained	Exon 4 of 7	NP_001293003.1	E7EUV9
	SLBP	NM_001306075.2		c.336C>G	p.Tyr112*	stop_gained	Exon 4 of 7	NP_001293004.1	Q14493-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLBP	ENST00000489418.6	TSL:1 MANE Select	c.453C>G	p.Tyr151*	stop_gained	Exon 5 of 8	ENSP00000417686.1	Q14493-1
	SLBP	ENST00000318386.8	TSL:3	c.474C>G	p.Tyr158*	stop_gained	Exon 5 of 8	ENSP00000316490.4	F8W8D3
	SLBP	ENST00000904664.1		c.444C>G	p.Tyr148*	stop_gained	Exon 5 of 8	ENSP00000574723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.64	D
PhyloP100		-0.0040
Vest4		0.86
ClinPred		0.85	D
GERP RS		-6.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=3/197	disease causing (fs/PTC)

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: rs2247341; hg19: chr4-1701317;