NM_001113491.2:c.19+89C>T

Variant names:

• chr17-77281643-C-T
• rs116581271
• NM_001113491.2:c.19+89C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001113491.2(SEPTIN9):​c.19+89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,307,100 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (19 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (10 hom.)
• Consequence: SEPTIN9 NM_001113491.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.464
• Publications: 0 publications found

Genes affected

SEPTIN9 (HGNC:7323): (septin 9) This gene is a member of the septin family involved in cytokinesis and cell cycle control. This gene is a candidate for the ovarian tumor suppressor gene. Mutations in this gene cause hereditary neuralgic amyotrophy, also known as neuritis with brachial predilection. A chromosomal translocation involving this gene on chromosome 17 and the MLL gene on chromosome 11 results in acute myelomonocytic leukemia. Multiple alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2009]

SEPTIN9-DT (HGNC:52818): (SEPTIN9 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-77281643-C-T is Benign according to our data. Variant chr17-77281643-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1220136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00753 (1146/152216) while in subpopulation AFR AF = 0.0253 (1051/41550). AF 95% confidence interval is 0.024. There are 19 homozygotes in GnomAd4. There are 557 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1146 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113491.2. 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
	SEPTIN9	NM_001113491.2	MANE Select	c.19+89C>T		intron	N/A	NP_001106963.1	Q9UHD8-1
	SEPTIN9	NM_001293695.2		c.19+89C>T		intron	N/A	NP_001280624.1	Q9UHD8-7
	SEPTIN9-DT	NR_136503.1		n.255G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN9	ENST00000427177.6	TSL:1 MANE Select	c.19+89C>T		intron	N/A	ENSP00000391249.1	Q9UHD8-1
	SEPTIN9	ENST00000873888.1		c.19+89C>T		intron	N/A	ENSP00000543947.1
	SEPTIN9	ENST00000873887.1		c.19+89C>T		intron	N/A	ENSP00000543946.1

Frequencies

GnomAD3 genomes AF: 0.00753 AC: 1145 AN: 152098 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.000681 AC: 787 AN: 1154884 Hom.: 10 Cov.: 15 AF XY: 0.000576 AC XY: 328 AN XY: 569900

African (AFR) AF: 0.0251 AC: 585 AN: 23284

American (AMR) AF: 0.00224 AC: 63 AN: 28160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20886

East Asian (EAS) AF: 0.00 AC: 0 AN: 28952

South Asian (SAS) AF: 0.00 AC: 0 AN: 67096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41886

Middle Eastern (MID) AF: 0.000692 AC: 3 AN: 4338

European-Non Finnish (NFE) AF: 0.0000494 AC: 44 AN: 891296

Other (OTH) AF: 0.00188 AC: 92 AN: 48986

GnomAD4 genome AF: 0.00753 AC: 1146 AN: 152216 Hom.: 19 Cov.: 33 AF XY: 0.00748 AC XY: 557 AN XY: 74420

African (AFR) AF: 0.0253 AC: 1051 AN: 41550

American (AMR) AF: 0.00477 AC: 73 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67994

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.00425 Hom.: 2

Bravo AF: 0.00930

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.8
DANN	Benign	0.93
PhyloP100		-0.46
PromoterAI		-0.038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs116581271; hg19: chr17-75277725;