Variant 22-19722938-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002688.6(SEPTIN5):c.*454G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 441,896 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 17 hom. )

Consequence

SEPTIN5
NM_002688.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

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:

SEPT5-GP1BB (HGNC:):

SEPT5-GP1BB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00392 (1134/289568) while in subpopulation SAS AF= 0.0224 (963/42896). AF 95% confidence interval is 0.0213. There are 17 homozygotes in gnomad4_exome. There are 840 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
SEPTIN5	NM_002688.6 linkuse as main transcript	c.*454G>C	3_prime_UTR_variant	12/12	ENST00000455784.7	NP_002679.2
SEPT5-GP1BB	NR_037611.1 linkuse as main transcript	n.3109G>C	non_coding_transcript_exon_variant	11/12
SEPTIN5	NM_001009939.3 linkuse as main transcript	c.*539G>C	3_prime_UTR_variant	11/11		NP_001009939.1
SEPT5-GP1BB	NR_037612.1 linkuse as main transcript	n.1613G>C	non_coding_transcript_exon_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN5	ENST00000455784.7 linkuse as main transcript	c.*454G>C		3_prime_UTR_variant	12/12	1	NM_002688.6	ENSP00000391311		Q99719-1

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0102

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00392

AC:

1134

AN:

289568

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

840

AN XY:

151036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00780

Gnomad4 SAS exome

AF:

0.0224

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000601

Gnomad4 OTH exome

AF:

0.000946

GnomAD4 genome

AF:

0.000945

AC:

144

AN:

152328

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000582

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.5

DANN

Benign

0.60

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over