Genetic Variant NM_018121.4:c.310G>T (chr10-100916695-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018121.4(SLF2):c.310G>T(p.Val104Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000042 in 1,547,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SLF2
NM_018121.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.23

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012277424).

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.310G>T	p.Val104Leu	missense	Exon 3 of 20	NP_060591.3
	SLF2	NM_001136123.2		c.310G>T	p.Val104Leu	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.310G>T	p.Val104Leu	missense	Exon 3 of 20	ENSP00000238961.3	Q8IX21-1
SLF2	ENST00000370269.3	TSL:1	c.310G>T	p.Val104Leu	missense	Exon 3 of 19	ENSP00000359292.3	Q8IX21-2
SLF2	ENST00000370271.7	TSL:1	c.310G>T	p.Val104Leu	missense	Exon 3 of 6	ENSP00000359294.3	B1AL16

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000516

AC:

AN:

193926

AF XY:

0.0000580

show subpopulations

Gnomad AFR exome

AF:

0.000644

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000294

AC:

AN:

1395134

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

689058

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

30712

American (AMR)

AF:

0.00

AC:

AN:

31062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21442

East Asian (EAS)

AF:

0.00

AC:

AN:

39332

South Asian (SAS)

AF:

0.00

AC:

AN:

72256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50744

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.00000644

AC:

AN:

1086682

Other (OTH)

AF:

0.0000522

AC:

AN:

57458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.000158

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

41524

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.084

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.13

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.62

M_CAP

Benign

0.0083

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

PhyloP100

-1.2

PrimateAI

Benign

0.27

PROVEAN

Benign

0.010

REVEL

Benign

0.010

Sift

Benign

0.096

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.13

MutPred

0.21

Gain of glycosylation at P106 (P = 0.1242)

MVP

0.14

MPC

0.15

ClinPred

0.044

GERP RS

-10

Varity_R

0.043

gMVP

0.041

Mutation Taster

=98/2

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over