NM_018121.4:c.41C>T

Variant names:

• chr10-100913151-C-T
• NM_018121.4:c.41C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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]

SLF2 Gene-Disease associations (from GenCC):

• Atelis syndrome 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, PanelApp Australia

ENSG00000272572 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018121.4. 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
	SLF2	NM_018121.4	MANE Select	c.41C>T	p.Ser14Leu	missense	Exon 1 of 20	NP_060591.3
	SLF2	NM_001136123.2		c.41C>T	p.Ser14Leu	missense	Exon 1 of 19	NP_001129595.1	Q8IX21-2
	SLF2	NM_001243770.2		c.41C>T	p.Ser14Leu	missense	Exon 1 of 1	NP_001230699.1	Q8IX21-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF2	ENST00000238961.9	TSL:1 MANE Select	c.41C>T	p.Ser14Leu	missense	Exon 1 of 20	ENSP00000238961.3	Q8IX21-1
	SLF2	ENST00000370269.3	TSL:1	c.41C>T	p.Ser14Leu	missense	Exon 1 of 19	ENSP00000359292.3	Q8IX21-2
	SLF2	ENST00000370271.7	TSL:1	c.41C>T	p.Ser14Leu	missense	Exon 1 of 6	ENSP00000359294.3	B1AL16

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.61	T
PhyloP100		3.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.20		Loss of phosphorylation at S14 (P = 0.0044)
MVP		0.68
MPC		0.62
ClinPred		0.94	D
GERP RS		5.3
PromoterAI		0.059	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.58
gMVP		0.29
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

hg19: chr10-102672908;