dbSNP rs781198806: SLFNL1:p.Glu263Lys (chr1-41017805-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144990.4(SLFNL1):c.787G>A(p.Glu263Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,601,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLFNL1
NM_144990.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Publications

0 publications found

Variant links:

Genes affected

SLFNL1 (HGNC:26313): (schlafen like 1) Predicted to enable ATP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SLFNL1 links:

SLFNL1-AS1 (HGNC:44126): (SLFNL1 antisense RNA 1)

SLFNL1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLFNL1	NM_144990.4	MANE Select	c.787G>A	p.Glu263Lys	missense	Exon 4 of 6	NP_659427.3
SLFNL1	NM_001168247.3		c.787G>A	p.Glu263Lys	missense	Exon 4 of 6	NP_001161719.1	Q499Z3-1
SLFNL1	NM_001377532.1		c.787G>A	p.Glu263Lys	missense	Exon 2 of 4	NP_001364461.1	Q499Z3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLFNL1	ENST00000302946.13	TSL:1 MANE Select	c.787G>A	p.Glu263Lys	missense	Exon 4 of 6	ENSP00000304401.8	Q499Z3-1
SLFNL1	ENST00000359345.5	TSL:1	c.787G>A	p.Glu263Lys	missense	Exon 2 of 4	ENSP00000352299.1	Q499Z3-1
SLFNL1-AS1	ENST00000626479.1	TSL:1	n.3216C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

GnomAD2 exomes

AF:

0.0000204

AC:

AN:

244900

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

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:

0.00000414

AC:

AN:

1449246

Hom.:

Cov.:

AF XY:

0.00000557

AC XY:

AN XY:

718772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33330

American (AMR)

AF:

0.000136

AC:

AN:

44252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25592

East Asian (EAS)

AF:

0.00

AC:

AN:

39408

South Asian (SAS)

AF:

0.00

AC:

AN:

85192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103314

Other (OTH)

AF:

0.00

AC:

AN:

59764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.0000131

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41598

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0093

Eigen

Benign

0.028

Eigen_PC

Benign

0.093

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.82

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

2.7

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

REVEL

Benign

0.19

Sift

Benign

0.14

Sift4G

Uncertain

0.038

Polyphen

0.68

Vest4

0.44

MutPred

0.76

Gain of ubiquitination at E263 (P = 0.0258)

MVP

0.39

MPC

0.095

ClinPred

0.54

GERP RS

5.4

Varity_R

0.079

gMVP

0.78

Mutation Taster

=90/10

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over