4-1711959-G-C

Position:

• chr4-1711959-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006527.4(SLBP):​c.91C>G​(p.Arg31Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLBP NM_006527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.553

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35262305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLBP	NM_006527.4	c.91C>G	p.Arg31Gly	missense_variant	2/8	ENST00000489418.6	NP_006518.1
SLBP	NM_001306074.2	c.91C>G	p.Arg31Gly	missense_variant	2/7		NP_001293003.1
SLBP	NM_001306075.2	c.59+171C>G		intron_variant			NP_001293004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLBP	ENST00000489418.6	c.91C>G	p.Arg31Gly	missense_variant	2/8	1	NM_006527.4	ENSP00000417686.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1168292 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 567234

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000756

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

Feb 21, 2024

The c.91C>G (p.R31G) alteration is located in exon 2 (coding exon 2) of the SLBP gene. This alteration results from a C to G substitution at nucleotide position 91, causing the arginine (R) at amino acid position 31 to be replaced by a glycine (G). 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	Uncertain	0.47
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.91	D;D;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.3	M;.;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0070	D;D;D
Sift4G	Benign	0.076	T;T;D
Polyphen		1.0	D;D;D
Vest4		0.30
MutPred		0.28		Loss of methylation at K32 (P = 0.052);Loss of methylation at K32 (P = 0.052);Loss of methylation at K32 (P = 0.052);
MVP		0.37
MPC		0.92
ClinPred		0.90	D
GERP RS		2.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.25
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1294338570; hg19: chr4-1713686;