rs370608296

Variant names:

• chr22-19714624-G-A
• rs370608296
• NM_002688.6:c.36G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.09
• Publications: 3 publications found

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]

ENSG00000304096 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002688.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN5	NM_002688.6	MANE Select	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 12	NP_002679.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN5	ENST00000455784.7	TSL:1 MANE Select	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 12	ENSP00000391311.2	Q99719-1
	SEPTIN5	ENST00000942371.1		c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 12	ENSP00000612430.1
	SEPTIN5	ENST00000406395.5	TSL:5	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 12	ENSP00000384535.1	E7EX32

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1031 AN: 150016 Hom.: 8 Cov.: 31

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

GnomAD2 exomes AF: 0.00582 AC: 607 AN: 104332 AF XY: 0.00586

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 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

African (AFR) AF: 0.00141 AC: 39 AN: 27640

American (AMR) AF: 0.00612 AC: 202 AN: 33000

Ashkenazi Jewish (ASJ) AF: 0.00422 AC: 101 AN: 23942

East Asian (EAS) AF: 0.00 AC: 0 AN: 32518

South Asian (SAS) AF: 0.000457 AC: 35 AN: 76512

European-Finnish (FIN) AF: 0.00468 AC: 168 AN: 35868

Middle Eastern (MID) AF: 0.00355 AC: 15 AN: 4222

European-Non Finnish (NFE) AF: 0.0111 AC: 11878 AN: 1065546

Other (OTH) AF: 0.00906 AC: 510 AN: 56302

GnomAD4 genome AF: 0.00687 AC: 1031 AN: 150114 Hom.: 8 Cov.: 31 AF XY: 0.00670 AC XY: 491 AN XY: 73320

African (AFR) AF: 0.00251 AC: 103 AN: 41004

American (AMR) AF: 0.0105 AC: 159 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00377 AC: 13 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5048

South Asian (SAS) AF: 0.00 AC: 0 AN: 4754

European-Finnish (FIN) AF: 0.00234 AC: 24 AN: 10252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0104 AC: 700 AN: 67156

Other (OTH) AF: 0.00526 AC: 11 AN: 2090

Alfa AF: 0.00708 Hom.: 7

Bravo AF: 0.00717

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		2.1
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs370608296; hg19: chr22-19702147;