Variant 4-1712166-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006527.4(SLBP):c.23C>T(p.Pro8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000549 in 1,234,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

SLBP
NM_006527.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

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]

SLBP links:

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ACMG classification

Classification made for transcript

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=0.16955504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLBP	NM_006527.4 linkuse as main transcript	c.23C>T	p.Pro8Leu	missense_variant	1/8	ENST00000489418.6	NP_006518.1	Q14493-1Q53XR2B3KSC5B3KST9
SLBP	NM_001306074.2 linkuse as main transcript	c.23C>T	p.Pro8Leu	missense_variant	1/7		NP_001293003.1	Q14493E7EUV9B4DUW7B3KST9
SLBP	NM_001306075.2 linkuse as main transcript	c.23C>T	p.Pro8Leu	missense_variant	1/7		NP_001293004.1	Q14493-2B3KST9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLBP	ENST00000489418.6 linkuse as main transcript	c.23C>T	p.Pro8Leu	missense_variant	1/8	1	NM_006527.4	ENSP00000417686.1		Q14493-1

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

151568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000442

Gnomad OTH

AF:

0.000481

GnomAD4 exome

AF:

0.000591

AC:

640

AN:

1082982

Hom.:

Cov.:

AF XY:

0.000599

AC XY:

309

AN XY:

515628

show subpopulations

Gnomad4 AFR exome

AF:

0.0000447

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000451

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000659

Gnomad4 OTH exome

AF:

0.000675

GnomAD4 genome

AF:

0.000251

AC:

AN:

151568

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

74028

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000442

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000212

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.23C>T (p.P8L) alteration is located in exon 1 (coding exon 1) of the SLBP gene. This alteration results from a C to T substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by a leucine (L). 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

0.16

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T;.;T

Eigen

Benign

-0.046

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.65

T;T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.1

M;M;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.095

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.025

D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D

Vest4

0.17

MutPred

0.18

Loss of glycosylation at P8 (P = 0.0127);Loss of glycosylation at P8 (P = 0.0127);Loss of glycosylation at P8 (P = 0.0127);Loss of glycosylation at P8 (P = 0.0127);

MVP

0.30

MPC

0.22

ClinPred

0.87

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over