rs10518992

Positions:

• chr15-58911416-T-C

Variant summary

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

The ENST00000380516.7(SLTM):​c.561+1147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,024 control chromosomes in the GnomAD database, including 3,319 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 0.20 (3319 hom., cov: 31)
• Consequence: SLTM ENST00000380516.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLTM	NM_024755.4	c.561+1147A>G		intron_variant		ENST00000380516.7	NP_079031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLTM	ENST00000380516.7	c.561+1147A>G		intron_variant		1	NM_024755.4	ENSP00000369887	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30290 AN: 151906 Hom.: 3321 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.199 AC: 30311 AN: 152024 Hom.: 3319 Cov.: 31 AF XY: 0.209 AC XY: 15509 AN XY: 74294

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.155

Alfa AF: 0.189 Hom.: 1895

Bravo AF: 0.187

Asia WGS AF: 0.383 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.71

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: rs10518992; hg19: chr15-59203615;