chr4-1694827-G-A

Position:

• chr4-1694827-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006527.4(SLBP):​c.643C>T​(p.Leu215Phe) variant causes a missense 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLBP NM_006527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25248215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLBP	NM_006527.4	c.643C>T	p.Leu215Phe	missense_variant	7/8	ENST00000489418.6	NP_006518.1
SLBP	NM_001306074.2	c.538C>T	p.Leu180Phe	missense_variant	6/7		NP_001293003.1
SLBP	NM_001306075.2	c.526C>T	p.Leu176Phe	missense_variant	6/7		NP_001293004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLBP	ENST00000489418.6	c.643C>T	p.Leu215Phe	missense_variant	7/8	1	NM_006527.4	ENSP00000417686.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.643C>T (p.L215F) alteration is located in exon 7 (coding exon 7) of the SLBP gene. This alteration results from a C to T substitution at nucleotide position 643, causing the leucine (L) at amino acid position 215 to be replaced by a phenylalanine (F). 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	0.13
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	.;T;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.77	T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	.;M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.056
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		0.99, 0.99	.;D;D;D
Vest4		0.44
MutPred		0.21		.;.;Loss of catalytic residue at L222 (P = 0.0423);.;
MVP		0.29
MPC		0.30
ClinPred		0.76	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-1696554;