chrX-119663551-C-T

Variant names:

• chrX-119663551-C-T
• rs1243232786
• NM_145799.4:c.272G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145799.4(SEPTIN6):​c.272G>A​(p.Ser91Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000928 in 1,077,548 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S91C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
• Consequence: SEPTIN6 NM_145799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.272G>A	p.Ser91Asn	missense	Exon 3 of 11	NP_665798.1	Q14141-2
	SEPTIN6	NM_015129.6		c.272G>A	p.Ser91Asn	missense	Exon 3 of 10	NP_055944.2
	SEPTIN6	NM_001410710.1		c.272G>A	p.Ser91Asn	missense	Exon 3 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.272G>A	p.Ser91Asn	missense	Exon 3 of 11	ENSP00000378108.1	Q14141-2
	SEPTIN6	ENST00000343984.5	TSL:1	c.272G>A	p.Ser91Asn	missense	Exon 3 of 10	ENSP00000341524.5	Q14141-1
	SEPTIN6	ENST00000354228.8	TSL:1	c.272G>A	p.Ser91Asn	missense	Exon 3 of 10	ENSP00000346169.4	Q14141-4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD2 exomes AF: 0.00000553 AC: 1 AN: 180749 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.28e-7 AC: 1 AN: 1077548 Hom.: 0 Cov.: 32 AF XY: 0.00000285 AC XY: 1 AN XY: 350846

African (AFR) AF: 0.00 AC: 0 AN: 25805

American (AMR) AF: 0.00 AC: 0 AN: 34402

Ashkenazi Jewish (ASJ) AF: 0.0000534 AC: 1 AN: 18726

East Asian (EAS) AF: 0.00 AC: 0 AN: 28571

South Asian (SAS) AF: 0.00 AC: 0 AN: 53405

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4011

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 829191

Other (OTH) AF: 0.00 AC: 0 AN: 44777

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Benign	0.23	T
Sift4G	Benign	0.58	T
Polyphen		0.78	P
Vest4		0.56
MVP		0.32
MPC		1.2
ClinPred		0.83	D
GERP RS		4.6
Varity_R		0.66
gMVP		0.50
Mutation Taster		=43/57	disease causing

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: rs1243232786; hg19: chrX-118797514;