Variant 5-94649596-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_032290.4(SLF1):c.737A>G(p.Gln246Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000936 in 1,468,618 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 8 hom. )

Consequence

SLF1
NM_032290.4 missense, splice_region

Scores

Splicing: ADA: 0.9984

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.07

Variant links:

Genes affected

SLF1 (HGNC:25408): (SMC5-SMC6 complex localization factor 1) 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 nucleoplasm and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

SLF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 5-94649596-A-G is Benign according to our data. Variant chr5-94649596-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLF1	NM_032290.4 linkuse as main transcript	c.737A>G	p.Gln246Arg	missense_variant, splice_region_variant	6/21	ENST00000265140.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLF1	ENST00000265140.10 linkuse as main transcript	c.737A>G	p.Gln246Arg	missense_variant, splice_region_variant	6/21	2	NM_032290.4	P1	Q9BQI6-1
SLF1	ENST00000466957.1 linkuse as main transcript	c.361-12702A>G		intron_variant, NMD_transcript_variant		5
SLF1	ENST00000508130.5 linkuse as main transcript	c.*34A>G		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	5/8	2			Q9BQI6-2

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00168

AC:

226

AN:

134766

Hom.:

AF XY:

0.00205

AC XY:

146

AN XY:

71104

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.000745

Gnomad ASJ exome

AF:

0.00164

Gnomad EAS exome

AF:

0.000208

Gnomad SAS exome

AF:

0.00889

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000614

Gnomad OTH exome

AF:

0.00159

GnomAD4 exome

AF:

0.000969

AC:

1275

AN:

1316292

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

755

AN XY:

641958

show subpopulations

Gnomad4 AFR exome

AF:

0.000437

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00132

Gnomad4 EAS exome

AF:

0.0000290

Gnomad4 SAS exome

AF:

0.00802

Gnomad4 FIN exome

AF:

0.0000213

Gnomad4 NFE exome

AF:

0.000567

Gnomad4 OTH exome

AF:

0.00115

GnomAD4 genome

AF:

0.000656

AC:

100

AN:

152326

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000791

Hom.:

Bravo

AF:

0.000533

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ExAC

AF:

0.00326

AC:

Asia WGS

AF:

0.00318

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

SLF1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.071

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.53

M_CAP

Benign

0.048

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.79

MutationTaster

Benign

0.53

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.54

REVEL

Benign

0.13

Sift

Benign

0.070

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.035

MVP

0.64

MPC

0.074

ClinPred

0.011

GERP RS

4.6

Varity_R

0.082

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.99

SpliceAI score (max)

0.56

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.56

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over