Genetic Variant SLFNL1:p.Ala382Val (chr1-41016185-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_144990.4(SLFNL1):c.1145C>T(p.Ala382Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

SLFNL1
NM_144990.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.20

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024001092).

BP6

Variant 1-41016185-G-A is Benign according to our data. Variant chr1-41016185-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2376249.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1145C>T	p.Ala382Val	missense	Exon 6 of 6	NP_659427.3
SLFNL1	NM_001168247.3		c.1145C>T	p.Ala382Val	missense	Exon 6 of 6	NP_001161719.1	Q499Z3-1
SLFNL1	NM_001377532.1		c.1145C>T	p.Ala382Val	missense	Exon 4 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.1145C>T	p.Ala382Val	missense	Exon 6 of 6	ENSP00000304401.8	Q499Z3-1
SLFNL1	ENST00000359345.5	TSL:1	c.1145C>T	p.Ala382Val	missense	Exon 4 of 4	ENSP00000352299.1	Q499Z3-1
SLFNL1-AS1	ENST00000626479.1	TSL:1	n.1596G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000358

AC:

AN:

251296

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000638

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000657

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41416

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

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:

0.0000386

Hom.:

Bravo

AF:

0.0000831

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.063

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.75

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.60

M_CAP

Benign

0.0017

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.5

PhyloP100

-1.2

PrimateAI

Benign

0.23

PROVEAN

Benign

0.54

REVEL

Benign

0.0070

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.024

MutPred

0.22

Loss of helix (P = 0.0138)

MVP

0.030

MPC

0.050

ClinPred

0.062

GERP RS

-3.8

Varity_R

0.035

gMVP

0.18

Mutation Taster

=95/5

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