rs12165395

Variant names:

• chr22-19715258-T-C
• rs12165395
• NM_002688.6:c.54+467T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002688.6(SEPTIN5):​c.54+467T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0425 in 152,322 control chromosomes in the GnomAD database, including 419 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 0.043 (419 hom., cov: 33)
• Consequence: SEPTIN5 NM_002688.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.946
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN5	NM_002688.6	c.54+467T>C		intron_variant	Intron 2 of 11	ENST00000455784.7	NP_002679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN5	ENST00000455784.7	c.54+467T>C		intron_variant	Intron 2 of 11	1	NM_002688.6	ENSP00000391311.2
SEPTIN5	ENST00000406395.5	c.54+467T>C		intron_variant	Intron 2 of 11	5		ENSP00000384535.1
SEPTIN5	ENST00000412544.5	c.-88+467T>C		intron_variant	Intron 1 of 9	5		ENSP00000408678.1
SEPTIN5	ENST00000406172.6	n.54+467T>C		intron_variant	Intron 2 of 9	5		ENSP00000385356.2

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6474 AN: 152204 Hom.: 419 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0425 AC: 6481 AN: 152322 Hom.: 419 Cov.: 33 AF XY: 0.0412 AC XY: 3069 AN XY: 74490

African (AFR) AF: 0.144 AC: 5973 AN: 41566

American (AMR) AF: 0.0131 AC: 201 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5180

South Asian (SAS) AF: 0.0190 AC: 92 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68032

Other (OTH) AF: 0.0345 AC: 73 AN: 2116

Alfa AF: 0.0242 Hom.: 407

Bravo AF: 0.0473

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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: rs12165395; hg19: chr22-19702781;