rs144625875

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_007241.4(SNF8):c.406G>A(p.Ala136Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000113 in 1,613,706 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 4 hom. )

Consequence

SNF8
NM_007241.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.54

Publications

3 publications found

Variant links:

Genes affected

SNF8 (HGNC:17028): (SNF8 subunit of ESCRT-II) The protein encoded by this gene is a component of the endosomal sorting complex required for transport II (ESCRT-II), which regulates the movement of ubiquitinylated transmembrane proteins to the lysosome for degradation. This complex also interacts with the RNA polymerase II elongation factor (ELL) to overcome the repressive effects of ELL on RNA polymerase II activity. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

SNF8 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy 115
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
neurodevelopmental disorder plus optic atrophy
Inheritance: AR Classification: MODERATE Submitted by: G2P, PanelApp Australia
complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SNF8 links:

ENSG00000230532 (HGNC:):

ENSG00000230532 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 3 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 1.1333 (below the threshold of 3.09). Trascript score misZ: 1.3894 (below the threshold of 3.09). GenCC associations: The gene is linked to neurodevelopmental disorder plus optic atrophy, complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.03630531).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007241.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNF8	NM_007241.4	MANE Select	c.406G>A	p.Ala136Thr	missense	Exon 5 of 8	NP_009172.2
SNF8	NM_001317192.2		c.406G>A	p.Ala136Thr	missense	Exon 5 of 8	NP_001304121.1	Q96H20-2
SNF8	NM_001317193.2		c.355G>A	p.Ala119Thr	missense	Exon 4 of 7	NP_001304122.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNF8	ENST00000502492.6	TSL:1 MANE Select	c.406G>A	p.Ala136Thr	missense	Exon 5 of 8	ENSP00000421380.1	Q96H20-1
SNF8	ENST00000290330.7	TSL:1	c.406G>A	p.Ala136Thr	missense	Exon 5 of 8	ENSP00000290330.3	Q96H20-2
SNF8	ENST00000956813.1		c.493G>A	p.Ala165Thr	missense	Exon 6 of 9	ENSP00000626872.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000207

AC:

AN:

251442

AF XY:

0.000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000117

AC:

171

AN:

1461454

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.000380

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39696

South Asian (SAS)

AF:

0.00145

AC:

125

AN:

86242

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111656

Other (OTH)

AF:

0.000166

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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:

0.0000722

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2112

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:

0.0000727

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

Uncertain

0.55

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.098

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

M_CAP

Benign

0.012

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.9

PhyloP100

5.5

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.5

REVEL

Benign

0.22

Sift

Benign

0.39

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.39

MVP

0.27

MPC

0.36

ClinPred

0.069

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.73

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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