Genetic Variant SLFNL1:p.Val260Met (chr1-41017814-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_144990.4(SLFNL1):c.778G>A(p.Val260Met) variant causes a missense change. The variant allele was found at a frequency of 0.000116 in 1,599,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V260L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SLFNL1
NM_144990.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.32

Publications

8 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 0 ACMG points.

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.778G>A	p.Val260Met	missense	Exon 4 of 6	NP_659427.3
SLFNL1	NM_001168247.3		c.778G>A	p.Val260Met	missense	Exon 4 of 6	NP_001161719.1	Q499Z3-1
SLFNL1	NM_001377532.1		c.778G>A	p.Val260Met	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.778G>A	p.Val260Met	missense	Exon 4 of 6	ENSP00000304401.8	Q499Z3-1
SLFNL1	ENST00000359345.5	TSL:1	c.778G>A	p.Val260Met	missense	Exon 2 of 4	ENSP00000352299.1	Q499Z3-1
SLFNL1-AS1	ENST00000626479.1	TSL:1	n.3225C>T		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

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:

0.000206

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.0000900

AC:

AN:

244344

AF XY:

0.0000682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000586

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000154

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000112

AC:

162

AN:

1446822

Hom.:

Cov.:

AF XY:

0.0000976

AC XY:

AN XY:

717076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33274

American (AMR)

AF:

0.000181

AC:

AN:

44214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25484

East Asian (EAS)

AF:

0.00

AC:

AN:

39334

South Asian (SAS)

AF:

0.0000588

AC:

AN:

85086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.000123

AC:

136

AN:

1101474

Other (OTH)

AF:

0.000218

AC:

AN:

59666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

152346

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.000523

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68024

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000170

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

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

Pathogenic

0.67

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

PhyloP100

5.3

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.93

REVEL

Benign

0.20

Sift

Uncertain

0.017

Sift4G

Pathogenic

0.0

Polyphen

0.96

Vest4

0.69

MVP

0.29

MPC

0.30

ClinPred

0.51

GERP RS

5.4

Varity_R

0.11

gMVP

0.65

Mutation Taster

=81/19

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