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GeneBe

22-19714624-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002688.6(SEPTIN5):c.36G>A(p.Ala12=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.09 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEPTIN5NM_002688.6 linkuse as main transcriptc.36G>A p.Ala12= synonymous_variant 1/12 ENST00000455784.7
LOC124905079XR_007068003.1 linkuse as main transcriptn.99+73C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEPTIN5ENST00000455784.7 linkuse as main transcriptc.36G>A p.Ala12= synonymous_variant 1/121 NM_002688.6 Q99719-1
SEPTIN5ENST00000406395.5 linkuse as main transcriptc.36G>A p.Ala12= synonymous_variant 1/125
SEPTIN5ENST00000406172.6 linkuse as main transcriptc.36G>A p.Ala12= synonymous_variant, NMD_transcript_variant 1/105

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00687
AC:
1031
AN:
150016
Hom.:
8
Cov.:
31
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.:
4
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.:
85
Cov.:
33
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00687
AC:
1031
AN:
150114
Hom.:
8
Cov.:
31
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.:
7
Bravo
AF:
0.00717

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeSep 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
12
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.

Other links and lift over

dbSNP: rs370608296; hg19: chr22-19702147; API