X-119629415-C-T

Variant names:

• chrX-119629415-C-T
• NM_145799.4:c.1183G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145799.4(SEPTIN6):​c.1183G>A​(p.Ala395Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: SEPTIN6 NM_145799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.98

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33444953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN6	NM_145799.4	c.1183G>A	p.Ala395Thr	missense_variant	Exon 9 of 11	ENST00000394610.7	NP_665798.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN6	ENST00000394610.7	c.1183G>A	p.Ala395Thr	missense_variant	Exon 9 of 11	1	NM_145799.4	ENSP00000378108.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1183G>A (p.A395T) alteration is located in exon 9 (coding exon 9) of the SEPT6 gene. This alteration results from a G to A substitution at nucleotide position 1183, causing the alanine (A) at amino acid position 395 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	.;.;.;T;.;T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.71	.;T;.;T;T;T
M_CAP	Pathogenic	0.53	D
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.75	N;N;N;.;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.30	T;T;T;T;T;T
Sift4G	Benign	0.57	T;T;T;T;T;T
Polyphen		0.0	.;.;.;.;.;B
Vest4		0.11
MVP		0.71
MPC		0.62
ClinPred		0.43	T
GERP RS		4.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.073
gMVP		0.092

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-118763378;