rs199739906

Variant names:

• chr7-35863614-C-G
• rs199739906
• NM_001788.6:c.232C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-35863614-C-G
• chr7-35863614-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001788.6(SEPTIN7):​c.232C>G​(p.Pro78Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P78S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SEPTIN7 NM_001788.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 0 publications found

Genes affected

SEPTIN7 (HGNC:1717): (septin 7) This gene encodes a protein that is highly similar to the CDC10 protein of Saccharomyces cerevisiae. The protein also shares similarity with Diff 6 of Drosophila and with H5 of mouse. Each of these similar proteins, including the yeast CDC10, contains a GTP-binding motif. The yeast CDC10 protein is a structural component of the 10 nm filament which lies inside the cytoplasmic membrane and is essential for cytokinesis. This human protein functions in gliomagenesis and in the suppression of glioma cell growth, and it is required for the association of centromere-associated protein E with the kinetochore. Alternative splicing results in multiple transcript variants. Several related pseudogenes have been identified on chromosomes 5, 7, 9, 10, 11, 14, 17 and 19. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14415535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6	c.232C>G	p.Pro78Ala	missense_variant	Exon 4 of 14	ENST00000350320.11	NP_001779.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN7	ENST00000350320.11	c.232C>G	p.Pro78Ala	missense_variant	Exon 4 of 14	5	NM_001788.6	ENSP00000344868.8
SEPTIN7	ENST00000635047.1	c.73C>G	p.Pro25Ala	missense_variant	Exon 4 of 7	4		ENSP00000489480.1
SEPTIN7	ENST00000635175.1	n.*149C>G		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000489192.1
SEPTIN7	ENST00000635175.1	n.*149C>G		3_prime_UTR_variant	Exon 4 of 14	2		ENSP00000489192.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1434972 Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1 AN XY: 714954

African (AFR) AF: 0.0000302 AC: 1 AN: 33152

American (AMR) AF: 0.00 AC: 0 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26020

East Asian (EAS) AF: 0.00 AC: 0 AN: 39454

South Asian (SAS) AF: 0.00 AC: 0 AN: 85784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104226

Other (OTH) AF: 0.0000167 AC: 1 AN: 59746

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Benign	0.033	.;T;T;T;.;T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.14	T;T;T;T;T;T
MetaSVM	Benign	-0.78	T
PhyloP100		1.2
PrimateAI	Uncertain	0.64	T
REVEL	Benign	0.050
Sift4G	Benign	0.31	T;T;T;T;T;T
Vest4		0.15
MutPred		0.38		.;Gain of sheet (P = 0.0125);.;.;.;.;
MVP		0.57
MPC		0.71
ClinPred		0.29	T
GERP RS		3.8
gMVP		0.46
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199739906; hg19: chr7-35903224;