4-77005782-A-G

Position:

• chr4-77005782-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018243.4(SEPTIN11):​c.324A>G​(p.Ile108Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEPTIN11 NM_018243.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.315

Genes affected

SEPTIN11 (HGNC:25589): (septin 11) SEPT11 belongs to the conserved septin family of filament-forming cytoskeletal GTPases that are involved in a variety of cellular functions including cytokinesis and vesicle trafficking (Hanai et al., 2004 [PubMed 15196925]; Nagata et al., 2004 [PubMed 15485874]).[supplied by OMIM, Jul 2009]

SEPTIN11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN11	NM_018243.4	c.324A>G	p.Ile108Met	missense_variant	3/10	ENST00000264893.11	NP_060713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN11	ENST00000264893.11	c.324A>G	p.Ile108Met	missense_variant	3/10	1	NM_018243.4	ENSP00000264893.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.324A>G (p.I108M) alteration is located in exon 3 (coding exon 3) of the SEPT11 gene. This alteration results from a A to G substitution at nucleotide position 324, causing the isoleucine (I) at amino acid position 108 to be replaced by a methionine (M). 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	0.30
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T;T;.;T;T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.047
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.7	M;.;.;.;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.5	D;D;D;D;D;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.085	T;T;T;T;T;T;T
Sift4G	Benign	0.067	T;T;T;T;T;T;T
Polyphen		0.55	P;.;.;.;P;.;.
Vest4		0.82
MutPred		0.79		Gain of disorder (P = 0.0619);Gain of disorder (P = 0.0619);.;Gain of disorder (P = 0.0619);.;.;.;
MVP		0.70
MPC		1.5
ClinPred		0.95	D
GERP RS		-0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.43

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: chr4-77926935;