10-100913151-C-T

Variant summary

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

The NM_018121.4(SLF2):c.41C>T(p.Ser14Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLF2 NM_018121.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57

Genes affected

SLF2 (HGNC:17814): (SMC5-SMC6 complex localization factor 2) Enables ubiquitin protein ligase binding activity. Involved in several processes, including positive regulation of cellular component organization; positive regulation of double-strand break repair; and protein localization to site of double-strand break. Located in chromatin; nucleoplasm; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31379217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLF2	NM_018121.4	c.41C>T	p.Ser14Leu	missense_variant	1/20	ENST00000238961.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLF2	ENST00000238961.9	c.41C>T	p.Ser14Leu	missense_variant	1/20	1	NM_018121.4	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.41C>T (p.S14L) alteration is located in exon 1 (coding exon 1) of the SLF2 gene. This alteration results from a C to T substitution at nucleotide position 41, causing the serine (S) at amino acid position 14 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.0037	T;T;.;.
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.61	T
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N;D;N;.
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;D;.;.
Vest4		0.44
MutPred		0.20		Loss of phosphorylation at S14 (P = 0.0044);Loss of phosphorylation at S14 (P = 0.0044);Loss of phosphorylation at S14 (P = 0.0044);Loss of phosphorylation at S14 (P = 0.0044);
MVP		0.68
MPC		0.62
ClinPred		0.94	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.58
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-102672908;