chr4-77030950-G-T

Position:

• chr4-77030950-G-T

Variant summary

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

The NM_018243.4(SEPTIN11):​c.1254G>T​(p.Lys418Asn) variant causes a missense change involving the alteration of a 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: 7.66

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.1254G>T	p.Lys418Asn	missense_variant	9/10	ENST00000264893.11	NP_060713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN11	ENST00000264893.11	c.1254G>T	p.Lys418Asn	missense_variant	9/10	1	NM_018243.4	ENSP00000264893.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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, 2023

The c.1254G>T (p.K418N) alteration is located in exon 9 (coding exon 9) of the SEPT11 gene. This alteration results from a G to T substitution at nucleotide position 1254, causing the lysine (K) at amino acid position 418 to be replaced by an asparagine (N). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;T;.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.43	T;T;T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.5	M;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.4	N;N;N;N;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Benign	0.063	T;T;T;T;D
Polyphen		0.98	D;.;.;D;.
Vest4		0.46
MutPred		0.18		Gain of glycosylation at T417 (P = 0.0068);Gain of glycosylation at T417 (P = 0.0068);Gain of glycosylation at T417 (P = 0.0068);.;.;
MVP		0.87
MPC		0.68
ClinPred		0.92	D
GERP RS		5.9
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.57
gMVP		0.50

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: chr4-77952103;