Genetic Variant SEPTIN6:p.Val100Ile (chrX-119663525-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_145799.4(SEPTIN6):c.298G>A(p.Val100Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,021,501 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 4 hem., cov: 21)

Exomes 𝑓: 0.000042 ( 0 hom. 10 hem. )

Consequence

SEPTIN6
NM_145799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56

Publications

0 publications found

Variant links:

Genes affected

SEPTIN6 (HGNC:15848): (septin 6) This gene is a member of the septin family of GTPases. Members of this family are required for cytokinesis. One version of pediatric acute myeloid leukemia is the result of a reciprocal translocation between chromosomes 11 and X, with the breakpoint associated with the genes encoding the mixed-lineage leukemia and septin 2 proteins. This gene encodes four transcript variants encoding three distinct isoforms. An additional transcript variant has been identified, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

SEPTIN6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12011221).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145799.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEPTIN6	NM_145799.4	MANE Select	c.298G>A	p.Val100Ile	missense	Exon 3 of 11	NP_665798.1	Q14141-2
SEPTIN6	NM_015129.6		c.298G>A	p.Val100Ile	missense	Exon 3 of 10	NP_055944.2
SEPTIN6	NM_001410710.1		c.298G>A	p.Val100Ile	missense	Exon 3 of 10	NP_001397639.1	B1AMS2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEPTIN6	ENST00000394610.7	TSL:1 MANE Select	c.298G>A	p.Val100Ile	missense	Exon 3 of 11	ENSP00000378108.1	Q14141-2
SEPTIN6	ENST00000343984.5	TSL:1	c.298G>A	p.Val100Ile	missense	Exon 3 of 10	ENSP00000341524.5	Q14141-1
SEPTIN6	ENST00000354228.8	TSL:1	c.298G>A	p.Val100Ile	missense	Exon 3 of 10	ENSP00000346169.4	Q14141-4

Frequencies

GnomAD3 genomes

AF:

0.000235

AC:

AN:

102181

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000667

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000426

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:

0.000714

GnomAD2 exomes

AF:

0.0000672

AC:

AN:

178659

AF XY:

0.0000157

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.0000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000746

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000424

AC:

AN:

919257

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

301837

show subpopulations

African (AFR)

AF:

0.000334

AC:

AN:

20930

American (AMR)

AF:

0.000136

AC:

AN:

29395

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12891

East Asian (EAS)

AF:

0.0000736

AC:

AN:

13585

South Asian (SAS)

AF:

0.00

AC:

AN:

51478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3252

European-Non Finnish (NFE)

AF:

0.0000357

AC:

AN:

728464

Other (OTH)

AF:

0.0000295

AC:

AN:

33924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000235

AC:

AN:

102244

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

AN XY:

28520

show subpopulations

African (AFR)

AF:

0.000666

AC:

AN:

28513

American (AMR)

AF:

0.000425

AC:

AN:

9404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2505

East Asian (EAS)

AF:

0.00

AC:

AN:

2792

South Asian (SAS)

AF:

0.00

AC:

AN:

1751

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4636

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50377

Other (OTH)

AF:

0.000705

AC:

AN:

1418

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

Genome Hom

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:

0.000142

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.12

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

1.7

PhyloP100

7.6

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.83

REVEL

Benign

0.16

Sift

Uncertain

0.019

Sift4G

Benign

0.15

Polyphen

0.0080

Vest4

0.51

MVP

0.31

MPC

0.53

ClinPred

0.088

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.44

gMVP

0.39

Mutation Taster

=99/1

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