Genetic Variant NM_018121.4:c.138C>G (chr10-100913248-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018121.4(SLF2):c.138C>G(p.Asp46Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLF2
NM_018121.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Publications

0 publications found

Variant links:

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

SLF2 links:

ENSG00000272572 (HGNC:):

ENSG00000272572 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24739432).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLF2	NM_018121.4	MANE Select	c.138C>G	p.Asp46Glu	missense splice_region	Exon 1 of 20	NP_060591.3
SLF2	NM_001243770.2		c.138C>G	p.Asp46Glu	missense	Exon 1 of 1	NP_001230699.1	Q8IX21-3
SLF2	NM_001136123.2		c.138C>G	p.Asp46Glu	missense splice_region	Exon 1 of 19	NP_001129595.1	Q8IX21-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLF2	ENST00000238961.9	TSL:1 MANE Select	c.138C>G	p.Asp46Glu	missense splice_region	Exon 1 of 20	ENSP00000238961.3	Q8IX21-1
SLF2	ENST00000370269.3	TSL:1	c.138C>G	p.Asp46Glu	missense splice_region	Exon 1 of 19	ENSP00000359292.3	Q8IX21-2
SLF2	ENST00000370271.7	TSL:1	c.138C>G	p.Asp46Glu	missense splice_region	Exon 1 of 6	ENSP00000359294.3	B1AL16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452666

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721974

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33102

American (AMR)

AF:

0.0000229

AC:

AN:

43612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25852

East Asian (EAS)

AF:

0.00

AC:

AN:

38966

South Asian (SAS)

AF:

0.00

AC:

AN:

84798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107894

Other (OTH)

AF:

0.00

AC:

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0063

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.75

M_CAP

Benign

0.019

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.64

PhyloP100

3.3

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.42

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Benign

0.14

Polyphen

1.0

Vest4

0.23

MutPred

0.083

Gain of solvent accessibility (P = 0.0638)

MVP

0.72

MPC

0.44

ClinPred

0.93

GERP RS

5.3

PromoterAI

-0.097

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.63

gMVP

0.11

Mutation Taster

=72/28

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over