X-119653028-G-A

Variant names:

• chrX-119653028-G-A
• rs186193225
• NM_145799.4:c.354C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_145799.4(SEPTIN6):​c.354C>T​(p.Ile118Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000854 in 1,206,270 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 7 hem., cov: 22)
  • Exomes 𝑓: 0.000081 (0 hom. 25 hem.)
• Consequence: SEPTIN6 NM_145799.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.60
• Publications: 0 publications found

Genes affected

SEPTIN6 (HGNC:15848): (septin 6) This gene is a member of the septin family of GTPases. Members of this family are required for cytokinesis. One version of pediatric acute myeloid leukemia is the result of a reciprocal translocation between chromosomes 11 and X, with the breakpoint associated with the genes encoding the mixed-lineage leukemia and septin 2 proteins. This gene encodes four transcript variants encoding three distinct isoforms. An additional transcript variant has been identified, but its biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant X-119653028-G-A is Benign according to our data. Variant chrX-119653028-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3054941.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145799.4. 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
	SEPTIN6	NM_145799.4	MANE Select	c.354C>T	p.Ile118Ile	synonymous	Exon 4 of 11	NP_665798.1	Q14141-2
	SEPTIN6	NM_015129.6		c.354C>T	p.Ile118Ile	synonymous	Exon 4 of 10	NP_055944.2
	SEPTIN6	NM_001410710.1		c.354C>T	p.Ile118Ile	synonymous	Exon 4 of 10	NP_001397639.1	B1AMS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN6	ENST00000394610.7	TSL:1 MANE Select	c.354C>T	p.Ile118Ile	synonymous	Exon 4 of 11	ENSP00000378108.1	Q14141-2
	SEPTIN6	ENST00000343984.5	TSL:1	c.354C>T	p.Ile118Ile	synonymous	Exon 4 of 10	ENSP00000341524.5	Q14141-1
	SEPTIN6	ENST00000354228.8	TSL:1	c.354C>T	p.Ile118Ile	synonymous	Exon 4 of 10	ENSP00000346169.4	Q14141-4

Frequencies

GnomAD3 genomes AF: 0.000117 AC: 13 AN: 110959 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000193

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00254

Gnomad SAS AF: 0.000379

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000237 AC: 43 AN: 181791 AF XY: 0.000211

Gnomad AFR exome AF: 0.0000761

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00289

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000247

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000813 AC: 89 AN: 1095257 Hom.: 0 Cov.: 29 AF XY: 0.0000693 AC XY: 25 AN XY: 360677

African (AFR) AF: 0.000114 AC: 3 AN: 26360

American (AMR) AF: 0.00 AC: 0 AN: 35138

Ashkenazi Jewish (ASJ) AF: 0.0000518 AC: 1 AN: 19305

East Asian (EAS) AF: 0.00119 AC: 36 AN: 30171

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 53952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40441

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.0000369 AC: 31 AN: 839824

Other (OTH) AF: 0.000370 AC: 17 AN: 45970

GnomAD4 genome AF: 0.000126 AC: 14 AN: 111013 Hom.: 0 Cov.: 22 AF XY: 0.000211 AC XY: 7 AN XY: 33215

African (AFR) AF: 0.00 AC: 0 AN: 30552

American (AMR) AF: 0.000193 AC: 2 AN: 10356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00283 AC: 10 AN: 3528

South Asian (SAS) AF: 0.000380 AC: 1 AN: 2634

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5899

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52984

Other (OTH) AF: 0.00 AC: 0 AN: 1512

Alfa AF: 0.000217 Hom.: 1

Bravo AF: 0.000128

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEPTIN6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.26
DANN	Benign	0.84
PhyloP100		-1.6
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: rs186193225; hg19: chrX-118786991;