Variant 22-19714624-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002688.6(SEPTIN5):c.36G>A(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,505,664 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0096 ( 85 hom. )

Consequence

SEPTIN5
NM_002688.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

SEPTIN5 (HGNC:9164): (septin 5) This gene is a member of the septin gene family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is mapped to 22q11, the region frequently deleted in DiGeorge and velocardiofacial syndromes. A translocation involving the MLL gene and this gene has also been reported in patients with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. The presence of a non-consensus polyA signal (AACAAT) in this gene also results in read-through transcription into the downstream neighboring gene (GP1BB; platelet glycoprotein Ib), whereby larger, non-coding transcripts are produced. [provided by RefSeq, Dec 2010]

SEPTIN5 links:

LOC124905079 (HGNC:):

LOC124905079 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 22-19714624-G-A is Benign according to our data. Variant chr22-19714624-G-A is described in ClinVar as [Benign]. Clinvar id is 774360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.09 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN5	NM_002688.6 link	c.36G>A	p.Ala12Ala	synonymous_variant	1/12	ENST00000455784.7	NP_002679.2	Q99719-1X5DNA9
LOC124905079	XR_007068003.1 link	n.99+73C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEPTIN5	ENST00000455784.7 link	c.36G>A	p.Ala12Ala	synonymous_variant	1/12	1	NM_002688.6	ENSP00000391311.2	Q99719-1
SEPTIN5	ENST00000406395.5 link	c.36G>A	p.Ala12Ala	synonymous_variant	1/12	5		ENSP00000384535.1	E7EX32
SEPTIN5	ENST00000406172.6 link	n.36G>A		non_coding_transcript_exon_variant	1/10	5		ENSP00000385356.2	E7EQM7

Frequencies

GnomAD3 genomes

AF:

0.00687

AC:

1031

AN:

150016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00252

Gnomad AMI

AF:

0.0233

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00234

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00531

GnomAD3 exomes

AF:

0.00582

AC:

607

AN:

104332

Hom.:

AF XY:

0.00586

AC XY:

342

AN XY:

58366

show subpopulations

Gnomad AFR exome

AF:

0.000961

Gnomad AMR exome

AF:

0.00626

Gnomad ASJ exome

AF:

0.00271

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000560

Gnomad FIN exome

AF:

0.00288

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00955

AC:

12948

AN:

1355550

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

6191

AN XY:

668964

show subpopulations

Gnomad4 AFR exome

AF:

0.00141

Gnomad4 AMR exome

AF:

0.00612

Gnomad4 ASJ exome

AF:

0.00422

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000457

Gnomad4 FIN exome

AF:

0.00468

Gnomad4 NFE exome

AF:

0.0111

Gnomad4 OTH exome

AF:

0.00906

GnomAD4 genome

AF:

0.00687

AC:

1031

AN:

150114

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

491

AN XY:

73320

show subpopulations

Gnomad4 AFR

AF:

0.00251

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00234

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.00708

Hom.:

Bravo

AF:

0.00717

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

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

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