chr15-58882340-G-T

Variant names:

• chr15-58882340-G-T
• rs7179456
• NM_024755.4:c.2996+1286C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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=-0.87).
• 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 rank	MANE	Protein	UniProt
SLTM	NM_024755.4	c.2996+1286C>A		intron_variant	Intron 20 of 20	ENST00000380516.7	NP_079031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLTM	ENST00000380516.7	c.2996+1286C>A		intron_variant	Intron 20 of 20	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

African (AFR) AF: 0.215 AC: 8898 AN: 41404

American (AMR) AF: 0.600 AC: 9154 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2280 AN: 3468

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5160

South Asian (SAS) AF: 0.446 AC: 2146 AN: 4808

European-Finnish (FIN) AF: 0.432 AC: 4537 AN: 10512

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44337 AN: 67918

Other (OTH) AF: 0.558 AC: 1178 AN: 2112

Alfa AF: 0.601 Hom.: 128252

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
PhyloP100		-0.056
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: rs7179456; hg19: chr15-59174539;