X-119653028-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_145799.4(SEPTIN6):​c.354C>A​(p.Ile118Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,258 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I118I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: SEPTIN6 NM_145799.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.

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>A	p.Ile118Ile	synonymous	Exon 4 of 11	NP_665798.1	Q14141-2
	SEPTIN6	NM_015129.6		c.354C>A	p.Ile118Ile	synonymous	Exon 4 of 10	NP_055944.2
	SEPTIN6	NM_001410710.1		c.354C>A	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>A	p.Ile118Ile	synonymous	Exon 4 of 11	ENSP00000378108.1	Q14141-2
	SEPTIN6	ENST00000343984.5	TSL:1	c.354C>A	p.Ile118Ile	synonymous	Exon 4 of 10	ENSP00000341524.5	Q14141-1
	SEPTIN6	ENST00000354228.8	TSL:1	c.354C>A	p.Ile118Ile	synonymous	Exon 4 of 10	ENSP00000346169.4	Q14141-4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095258 Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 1 AN XY: 360678

African (AFR) AF: 0.00 AC: 0 AN: 26360

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19305

East Asian (EAS) AF: 0.00 AC: 0 AN: 30172

South Asian (SAS) AF: 0.00 AC: 0 AN: 53952

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

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4096

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839824

Other (OTH) AF: 0.00 AC: 0 AN: 45970

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.22
DANN	Benign	0.78
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;