chrX-119652962-T-G

Variant names:

• chrX-119652962-T-G
• rs373846041
• NM_145799.4:c.420A>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_145799.4(SEPTIN6):​c.420A>C​(p.Leu140Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,206,916 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.000075 (0 hom. 26 hem.)
• Consequence: SEPTIN6 NM_145799.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.272
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-119652962-T-G is Benign according to our data. Variant chrX-119652962-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2661300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.272 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 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.420A>C	p.Leu140Leu	synonymous	Exon 4 of 11	NP_665798.1	Q14141-2
	SEPTIN6	NM_015129.6		c.420A>C	p.Leu140Leu	synonymous	Exon 4 of 10	NP_055944.2
	SEPTIN6	NM_001410710.1		c.420A>C	p.Leu140Leu	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.420A>C	p.Leu140Leu	synonymous	Exon 4 of 11	ENSP00000378108.1	Q14141-2
	SEPTIN6	ENST00000343984.5	TSL:1	c.420A>C	p.Leu140Leu	synonymous	Exon 4 of 10	ENSP00000341524.5	Q14141-1
	SEPTIN6	ENST00000354228.8	TSL:1	c.420A>C	p.Leu140Leu	synonymous	Exon 4 of 10	ENSP00000346169.4	Q14141-4

Frequencies

GnomAD3 genomes AF: 0.0000634 AC: 7 AN: 110468 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000327 AC: 6 AN: 183458 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000732

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000748 AC: 82 AN: 1096448 Hom.: 0 Cov.: 29 AF XY: 0.0000719 AC XY: 26 AN XY: 361850

African (AFR) AF: 0.00 AC: 0 AN: 26366

American (AMR) AF: 0.00 AC: 0 AN: 35204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54099

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.0000940 AC: 79 AN: 840498

Other (OTH) AF: 0.0000652 AC: 3 AN: 46039

GnomAD4 genome AF: 0.0000634 AC: 7 AN: 110468 Hom.: 0 Cov.: 22 AF XY: 0.0000612 AC XY: 2 AN XY: 32660

African (AFR) AF: 0.00 AC: 0 AN: 30427

American (AMR) AF: 0.00 AC: 0 AN: 10221

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3514

South Asian (SAS) AF: 0.00 AC: 0 AN: 2601

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 52880

Other (OTH) AF: 0.00 AC: 0 AN: 1484

Alfa AF: 0.000174 Hom.: 1

Bravo AF: 0.0000718

EpiCase AF: 0.000164

EpiControl AF: 0.000237

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	-0.55
CADD	Benign	9.7
DANN	Benign	0.71
PhyloP100		0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs373846041; hg19: chrX-118786925;