Genetic Variant SEPTIN3:p.Gln754Gln (chr22-41992666-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363845.2(SEPTIN3):c.2262G>A(p.Gln754Gln) variant causes a splice region, synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,599,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEPTIN3
NM_001363845.2 splice_region, synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.62

Publications

0 publications found

Variant links:

Genes affected

SEPTIN3 (HGNC:10750): (septin 3) This gene belongs to the septin family of GTPases. Members of this family are required for cytokinesis. Expression is upregulated by retinoic acid in a human teratocarcinoma cell line. The specific function of this gene has not been determined. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2018]

SEPTIN3 links:

ENSG00000301540 (HGNC:):

ENSG00000301540 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363845.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SEPTIN3	NM_001363845.2	MANE Select	c.2262G>A	p.Gln754Gln	splice_region synonymous	Exon 9 of 12	NP_001350774.1
SEPTIN3	NM_001389668.1		c.2262G>A	p.Gln754Gln	splice_region synonymous	Exon 9 of 11	NP_001376597.1
SEPTIN3	NM_001389669.1		c.2133G>A	p.Gln711Gln	splice_region synonymous	Exon 8 of 11	NP_001376598.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SEPTIN3	ENST00000644076.2	MANE Select	c.2262G>A	p.Gln754Gln	splice_region synonymous	Exon 9 of 12	ENSP00000494051.1
SEPTIN3	ENST00000396426.7	TSL:1	c.768G>A	p.Gln256Gln	splice_region synonymous	Exon 8 of 11	ENSP00000379704.3
SEPTIN3	ENST00000396425.8	TSL:1	c.768G>A	p.Gln256Gln	splice_region synonymous	Exon 8 of 10	ENSP00000379703.3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000418

AC:

AN:

238990

AF XY:

0.00000778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000922

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1447574

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718416

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33246

American (AMR)

AF:

0.00

AC:

AN:

43418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25374

East Asian (EAS)

AF:

0.00

AC:

AN:

39396

South Asian (SAS)

AF:

0.00

AC:

AN:

83758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1103840

Other (OTH)

AF:

0.00

AC:

AN:

59902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

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:

0.0000285

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

9.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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