rs191011663

Variant names:

• chr17-58520745-C-G
• rs191011663
• NM_001368771.2:c.2929G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-58520745-C-G
• chr17-58520745-C-T

Variant summary

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

The NM_001368771.2(SEPTIN4):​c.2929G>C​(p.Glu977Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SEPTIN4 NM_001368771.2 missense, splice_region
• Scores: Splicing: ADA: 0.002104
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84

Genes affected

SEPTIN4 (HGNC:9165): (septin 4) This gene is a member of the septin family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse, and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is highly expressed in brain and heart. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. One of the isoforms (known as ARTS) is distinct; it is localized to the mitochondria, and has a role in apoptosis and cancer. [provided by RefSeq, Nov 2010]

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

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 rank	MANE	Protein	UniProt
SEPTIN4	NM_001368771.2	c.2929G>C	p.Glu977Gln	missense_variant, splice_region_variant	Exon 13 of 14	ENST00000672673.2	NP_001355700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN4	ENST00000672673.2	c.2929G>C	p.Glu977Gln	missense_variant, splice_region_variant	Exon 13 of 14		NM_001368771.2	ENSP00000500383.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Uncertain	0.60	.;.;D;.;T;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;.;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.2	.;.;M;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	N;.;N;.;.;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D;.;D;.;.;D;D
Sift4G	Uncertain	0.0050	D;T;D;D;T;D;D
Polyphen		1.0	D;D;D;D;.;D;D
Vest4		0.66
MutPred		0.28		.;.;Gain of helix (P = 0.0199);.;.;.;.;
MVP		0.92
MPC		1.3
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.47
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.050
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

LitVar

Other links and lift over

dbSNP: rs191011663; hg19: chr17-56598106;