rs201949343

Variant names:

• chr17-58525722-G-A
• rs201949343
• NM_001368771.2:c.2065C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58525722-G-A
• chr17-58525722-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001368771.2(SEPTIN4):​c.2065C>T​(p.Arg689Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: SEPTIN4 NM_001368771.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41613847).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368771.2. 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
	SEPTIN4	NM_001368771.2	MANE Select	c.2065C>T	p.Arg689Trp	missense	Exon 6 of 14	NP_001355700.1	O43236-7
	SEPTIN4	NM_001256782.2		c.556C>T	p.Arg186Trp	missense	Exon 5 of 13	NP_001243711.1	O43236-4
	SEPTIN4	NM_004574.5		c.511C>T	p.Arg171Trp	missense	Exon 4 of 12	NP_004565.1	O43236-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPTIN4	ENST00000672673.2	MANE Select	c.2065C>T	p.Arg689Trp	missense	Exon 6 of 14	ENSP00000500383.1	O43236-7
	SEPTIN4	ENST00000317268.7	TSL:1	c.511C>T	p.Arg171Trp	missense	Exon 4 of 12	ENSP00000321674.3	O43236-1
	SEPTIN4	ENST00000317256.10	TSL:1	c.454C>T	p.Arg152Trp	missense	Exon 4 of 12	ENSP00000321071.6	O43236-2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

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: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000131 AC: 33 AN: 251478 AF XY: 0.000118

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1461832 Hom.: 0 Cov.: 30 AF XY: 0.0000619 AC XY: 45 AN XY: 727214

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00110 AC: 59 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74300

African (AFR) AF: 0.000217 AC: 9 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000238 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

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	0.27
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.7
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.97	D
Vest4		0.49
MVP		0.88
MPC		0.97
ClinPred		0.59	D
GERP RS		4.9
Varity_R		0.43
gMVP		0.56
Mutation Taster		=83/17	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: rs201949343; hg19: chr17-56603083;