rs12595482

Variant names:

• chr15-58903480-G-A
• rs12595482
• NM_024755.4:c.562-2193C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024755.4(SLTM):​c.562-2193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 147,196 control chromosomes in the GnomAD database, including 3,108 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 (3108 hom., cov: 27)
• Consequence: SLTM NM_024755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024755.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLTM	NM_024755.4	MANE Select	c.562-2193C>T		intron	N/A	NP_079031.2	Q9NWH9-1
	SLTM	NM_001013843.3		c.562-2193C>T		intron	N/A	NP_001013865.1
	SLTM	NR_135042.2		n.478-2193C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLTM	ENST00000380516.7	TSL:1 MANE Select	c.562-2193C>T		intron	N/A	ENSP00000369887.2	Q9NWH9-1
	SLTM	ENST00000970319.1		c.685-2193C>T		intron	N/A	ENSP00000640378.1
	SLTM	ENST00000924228.1		c.562-2193C>T		intron	N/A	ENSP00000594287.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29068 AN: 147114 Hom.: 3110 Cov.: 27

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0653

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.198 AC: 29085 AN: 147196 Hom.: 3108 Cov.: 27 AF XY: 0.207 AC XY: 14810 AN XY: 71464

African (AFR) AF: 0.174 AC: 6989 AN: 40096

American (AMR) AF: 0.190 AC: 2749 AN: 14506

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 541 AN: 3416

East Asian (EAS) AF: 0.414 AC: 2045 AN: 4936

South Asian (SAS) AF: 0.446 AC: 2059 AN: 4616

European-Finnish (FIN) AF: 0.287 AC: 2774 AN: 9682

Middle Eastern (MID) AF: 0.139 AC: 40 AN: 288

European-Non Finnish (NFE) AF: 0.173 AC: 11521 AN: 66722

Other (OTH) AF: 0.151 AC: 309 AN: 2046

Alfa AF: 0.187 Hom.: 1571

Bravo AF: 0.182

Asia WGS AF: 0.381 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12595482; hg19: chr15-59195679;