7-35863614-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001788.6(SEPTIN7):​c.232C>T​(p.Pro78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,587,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00068 (0 hom.)
• Consequence: SEPTIN7 NM_001788.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04465255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6	c.232C>T	p.Pro78Ser	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>T	p.Pro78Ser	missense_variant	Exon 4 of 14	5	NM_001788.6	ENSP00000344868.8
SEPTIN7	ENST00000635047.1	c.73C>T	p.Pro25Ser	missense_variant	Exon 4 of 7	4		ENSP00000489480.1
SEPTIN7	ENST00000635175.1	n.*149C>T		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000489192.1
SEPTIN7	ENST00000635175.1	n.*149C>T		3_prime_UTR_variant	Exon 4 of 14	2		ENSP00000489192.1

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 151974 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000287 AC: 66 AN: 229666 AF XY: 0.000260

Gnomad AFR exome AF: 0.0000724

Gnomad AMR exome AF: 0.0000591

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000541

Gnomad OTH exome AF: 0.000344

GnomAD4 exome AF: 0.000675 AC: 969 AN: 1434950 Hom.: 0 Cov.: 27 AF XY: 0.000670 AC XY: 479 AN XY: 714948

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

American (AMR) AF: 0.000112 AC: 5 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26020

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

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85784

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

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4114

European-Non Finnish (NFE) AF: 0.000840 AC: 927 AN: 1104206

Other (OTH) AF: 0.000519 AC: 31 AN: 59746

GnomAD4 genome AF: 0.000375 AC: 57 AN: 152092 Hom.: 0 Cov.: 30 AF XY: 0.000336 AC XY: 25 AN XY: 74340

African (AFR) AF: 0.0000723 AC: 3 AN: 41500

American (AMR) AF: 0.000131 AC: 2 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000175 Hom.: 0

Bravo AF: 0.000457

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000974 AC: 4

ExAC AF: 0.000237 AC: 27

EpiCase AF: 0.00104

EpiControl AF: 0.000477

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232C>T (p.P78S) alteration is located in exon 4 (coding exon 4) of the SEPT7 gene. This alteration results from a C to T substitution at nucleotide position 232, causing the proline (P) at amino acid position 78 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	.;T;T;T;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.045	T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
PhyloP100		1.2
PrimateAI	Uncertain	0.64	T
REVEL	Benign	0.035
Sift4G	Benign	0.25	T;T;T;T;T;T
Vest4		0.12
MVP		0.54
MPC		0.74
ClinPred		0.019	T
GERP RS		3.8
gMVP		0.52
Mutation Taster		=84/16	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: rs199739906; hg19: chr7-35903224;