22-19722938-G-C

Variant names:

• chr22-19722938-G-C
• rs3810596
• NM_002688.6:c.*454G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380
• Publications: 1 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]

ENSG00000284874 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 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 GnomAdExome4. There are 840 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 17 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.*454G>C		3_prime_UTR	Exon 12 of 12	NP_002679.2
	SEPTIN5	NM_001009939.3		c.*539G>C		3_prime_UTR	Exon 11 of 11	NP_001009939.1	Q99719-2
	SEPT5-GP1BB	NR_037611.1		n.3109G>C		non_coding_transcript_exon	Exon 11 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN5	ENST00000455784.7	TSL:1 MANE Select	c.*454G>C		3_prime_UTR	Exon 12 of 12	ENSP00000391311.2	Q99719-1
	ENSG00000284874	ENST00000431044.5	TSL:1	n.*454G>C		non_coding_transcript_exon	Exon 11 of 12	ENSP00000399685.1	F6X4M4
	ENSG00000284874	ENST00000455843.5	TSL:1	n.*454G>C		non_coding_transcript_exon	Exon 11 of 12	ENSP00000391731.1	G3XAH0

Frequencies

GnomAD3 genomes AF: 0.000946 AC: 144 AN: 152210 Hom.: 0 Cov.: 33

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.: 17 Cov.: 0 AF XY: 0.00556 AC XY: 840 AN XY: 151036

African (AFR) AF: 0.00 AC: 0 AN: 9436

American (AMR) AF: 0.00 AC: 0 AN: 13824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9930

East Asian (EAS) AF: 0.00780 AC: 154 AN: 19746

South Asian (SAS) AF: 0.0224 AC: 963 AN: 42896

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1200

European-Non Finnish (NFE) AF: 0.00000601 AC: 1 AN: 166350

Other (OTH) AF: 0.000946 AC: 16 AN: 16906

GnomAD4 genome AF: 0.000945 AC: 144 AN: 152328 Hom.: 0 Cov.: 33 AF XY: 0.00133 AC XY: 99 AN XY: 74496

African (AFR) AF: 0.0000240 AC: 1 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5186

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000582

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.5
DANN	Benign	0.60
PhyloP100		0.038
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

Other links and lift over

dbSNP: rs3810596; hg19: chr22-19710461;