15-58882340-G-T

Position:

• chr15-58882340-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024755.4(SLTM):​c.2996+1286C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,828 control chromosomes in the GnomAD database, including 21,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (21340 hom., cov: 30)
• Consequence: SLTM NM_024755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

Genes affected

SLTM (HGNC:20709): (SAFB like transcription modulator) Enables RNA binding activity. Predicted to be involved in regulation of mRNA processing and regulation of transcription by RNA polymerase II. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

RNF111 (HGNC:17384): (ring finger protein 111) The protein encoded by this gene is a nuclear RING-domain containing E3 ubiquitin ligase. This protein interacts with the transforming growth factor (TGF) -beta/NODAL signaling pathway by promoting the ubiquitination and proteosomal degradation of negative regulators, like SMAD proteins, and thereby enhances TGF-beta target-gene transcription. As a modulator of the nodal signaling cascade, this gene plays a critical role in the induction of mesoderm during embryonic development. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

SLTM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLTM	NM_024755.4	c.2996+1286C>A		intron_variant		ENST00000380516.7	NP_079031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLTM	ENST00000380516.7	c.2996+1286C>A		intron_variant		1	NM_024755.4	ENSP00000369887.2

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74900 AN: 151710 Hom.: 21345 Cov.: 30

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.601

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.558

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.493 AC: 74901 AN: 151828 Hom.: 21340 Cov.: 30 AF XY: 0.487 AC XY: 36120 AN XY: 74204

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.558

Alfa AF: 0.626 Hom.: 66554

Bravo AF: 0.491

Asia WGS AF: 0.345 AC: 1202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs7179456; hg19: chr15-59174539;