chr15-58887316-G-T

Position:

• chr15-58887316-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_024755.4(SLTM):​c.2600C>A​(p.Pro867His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLTM NM_024755.4 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.52

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-58887316-G-T is Pathogenic according to our data. Variant chr15-58887316-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 617857.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.055332214). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLTM	NM_024755.4	c.2600C>A	p.Pro867His	missense_variant	18/21	ENST00000380516.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLTM	ENST00000380516.7	c.2600C>A	p.Pro867His	missense_variant	18/21	1	NM_024755.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Jeune thoracic dystrophy Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.078
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.39	T;T
Polyphen		0.22	B;.
Vest4		0.41
MutPred		0.11		Gain of MoRF binding (P = 0.0719);.;
MVP		0.068
MPC		1.5
ClinPred		0.24	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.11

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: rs1401798992; hg19: chr15-59179515;