15-58907738-T-G

Variant names:

• chr15-58907738-T-G
• rs17302045
• NM_024755.4:c.561+4825A>C

Variant summary

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

The NM_024755.4(SLTM):​c.561+4825A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,038 control chromosomes in the GnomAD database, including 40,443 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 0.72 (40443 hom., cov: 32)
• Consequence: SLTM NM_024755.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLTM	NM_024755.4	c.561+4825A>C		intron_variant	Intron 5 of 20	ENST00000380516.7	NP_079031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLTM	ENST00000380516.7	c.561+4825A>C		intron_variant	Intron 5 of 20	1	NM_024755.4	ENSP00000369887.2

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109284 AN: 151920 Hom.: 40440 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.719 AC: 109320 AN: 152038 Hom.: 40443 Cov.: 32 AF XY: 0.713 AC XY: 52989 AN XY: 74332

African (AFR) AF: 0.538 AC: 22298 AN: 41430

American (AMR) AF: 0.785 AC: 12004 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2885 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3077 AN: 5166

South Asian (SAS) AF: 0.563 AC: 2714 AN: 4822

European-Finnish (FIN) AF: 0.718 AC: 7573 AN: 10554

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56009 AN: 68000

Other (OTH) AF: 0.787 AC: 1660 AN: 2110

Alfa AF: 0.808 Hom.: 53699

Bravo AF: 0.721

Asia WGS AF: 0.587 AC: 2046 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	6.9
DANN	Benign	0.73
PhyloP100		-0.13
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: rs17302045; hg19: chr15-59199937;