Genetic Variant NM_145799.4:c.1202C>T (chrX-119629396-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_145799.4(SEPTIN6):c.1202C>T(p.Thr401Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,209,729 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 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 0.000036 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 7 hem. )

Consequence

SEPTIN6
NM_145799.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

Publications

1 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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3557753).

BS2

High Hemizygotes in GnomAdExome4 at 7 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.1202C>T	p.Thr401Met	missense	Exon 9 of 11	NP_665798.1	Q14141-2
SEPTIN6	NM_015129.6		c.1202C>T	p.Thr401Met	missense	Exon 9 of 10	NP_055944.2
SEPTIN6	NM_001410710.1		c.1202C>T	p.Thr401Met	missense	Exon 9 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.1202C>T	p.Thr401Met	missense	Exon 9 of 11	ENSP00000378108.1	Q14141-2
SEPTIN6	ENST00000343984.5	TSL:1	c.1202C>T	p.Thr401Met	missense	Exon 9 of 10	ENSP00000341524.5	Q14141-1
SEPTIN6	ENST00000354228.8	TSL:1	c.1202C>T	p.Thr401Met	missense	Exon 9 of 10	ENSP00000346169.4	Q14141-4

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112047

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000436

AC:

AN:

183446

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1097682

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363052

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26396

American (AMR)

AF:

0.000170

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19381

East Asian (EAS)

AF:

0.0000662

AC:

AN:

30202

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54121

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4094

European-Non Finnish (NFE)

AF:

0.0000166

AC:

AN:

841711

Other (OTH)

AF:

0.0000434

AC:

AN:

46070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

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:

0.0000357

AC:

AN:

112047

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34221

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30827

American (AMR)

AF:

0.000191

AC:

AN:

10485

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2653

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2739

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6119

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53201

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

0.075

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.36

MetaSVM

Uncertain

0.030

MutationAssessor

Benign

0.55

PhyloP100

7.8

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.55

REVEL

Uncertain

0.36

Sift

Uncertain

0.027

Sift4G

Uncertain

0.042

Polyphen

0.97

Vest4

0.21

MVP

0.75

MPC

0.66

ClinPred

0.27

GERP RS

5.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.12

gMVP

0.24

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over