NM_001363845.2:c.2162G>A

Variant names:

• chr22-41989683-G-A
• NM_001363845.2:c.2162G>A

Variant summary

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

The NM_001363845.2(SEPTIN3):​c.2162G>A​(p.Arg721Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SEPTIN3 NM_001363845.2 missense, splice_region
• Scores: Splicing: ADA: 0.9658
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.90
• Publications: 0 publications found

Genes affected

SEPTIN3 (HGNC:10750): (septin 3) This gene belongs to the septin family of GTPases. Members of this family are required for cytokinesis. Expression is upregulated by retinoic acid in a human teratocarcinoma cell line. The specific function of this gene has not been determined. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2018]

ENSG00000301540 (HGNC:):

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_001363845.2. 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
	SEPTIN3	NM_001363845.2	MANE Select	c.2162G>A	p.Arg721Lys	missense splice_region	Exon 7 of 12	NP_001350774.1	A0A2R8Y4H2
	SEPTIN3	NM_001389668.1		c.2162G>A	p.Arg721Lys	missense splice_region	Exon 7 of 11	NP_001376597.1
	SEPTIN3	NM_001389669.1		c.2033G>A	p.Arg678Lys	missense splice_region	Exon 6 of 11	NP_001376598.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN3	ENST00000644076.2	MANE Select	c.2162G>A	p.Arg721Lys	missense splice_region	Exon 7 of 12	ENSP00000494051.1	A0A2R8Y4H2
	SEPTIN3	ENST00000396426.7	TSL:1	c.668G>A	p.Arg223Lys	missense splice_region	Exon 6 of 11	ENSP00000379704.3	Q9UH03-1
	SEPTIN3	ENST00000396425.8	TSL:1	c.668G>A	p.Arg223Lys	missense splice_region	Exon 6 of 10	ENSP00000379703.3	Q9UH03-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 31

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	0.11
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.29	T
Sift4G	Benign	0.35	T
Polyphen		0.98	D
Vest4		0.26
MutPred		0.61		Loss of ubiquitination at K226 (P = 0.0756)
MVP		0.69
MPC		0.95
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.60
gMVP		0.78
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Benign	0.63
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

hg19: chr22-42385687;