chr4-1703638-T-C

Position:

• chr4-1703638-T-C

Variant summary

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

The NM_006527.4(SLBP):​c.239A>G​(p.Glu80Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.74

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLBP	NM_006527.4	c.239A>G	p.Glu80Gly	missense_variant	3/8	ENST00000489418.6	NP_006518.1
SLBP	NM_001306075.2	c.122A>G	p.Glu41Gly	missense_variant	2/7		NP_001293004.1
SLBP	NM_001306074.2	c.177-3568A>G		intron_variant			NP_001293003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLBP	ENST00000489418.6	c.239A>G	p.Glu80Gly	missense_variant	3/8	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

Jul 05, 2023

The c.239A>G (p.E80G) alteration is located in exon 3 (coding exon 3) of the SLBP gene. This alteration results from a A to G substitution at nucleotide position 239, causing the glutamic acid (E) at amino acid position 80 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	.;T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.99, 1.0	.;D;D
Vest4		0.76
MutPred		0.20		.;Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP		0.27
MPC		0.37
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.37
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr4-1705365;