Genetic Variant NM_018121.4:c.401C>T (chr10-100916786-C-T) – 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.401C>T(p.Pro134Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SLF2
NM_018121.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.490

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:

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=0.20256779).

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.401C>T	p.Pro134Leu	missense	Exon 3 of 20	NP_060591.3
	SLF2	NM_001136123.2		c.401C>T	p.Pro134Leu	missense	Exon 3 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.401C>T	p.Pro134Leu	missense	Exon 3 of 20	ENSP00000238961.3	Q8IX21-1
SLF2	ENST00000370269.3	TSL:1	c.401C>T	p.Pro134Leu	missense	Exon 3 of 19	ENSP00000359292.3	Q8IX21-2
SLF2	ENST00000370271.7	TSL:1	c.401C>T	p.Pro134Leu	missense	Exon 3 of 6	ENSP00000359294.3	B1AL16

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111842

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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.:

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

0.11

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0014

Eigen

Benign

0.093

Eigen_PC

Benign

0.041

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.018

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.87

PhyloP100

0.49

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.94

REVEL

Benign

0.18

Sift

Benign

0.33

Sift4G

Benign

0.43

Polyphen

1.0

Vest4

0.31

MutPred

0.41

Loss of catalytic residue at P134 (P = 0.0031)

MVP

0.37

MPC

0.16

ClinPred

0.79

GERP RS

4.6

Varity_R

0.074

gMVP

0.17

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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