chr7-35863614-C-T

Position:

• chr7-35863614-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 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. 11/16 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

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]

SEPTIN7 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04465255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN7	NM_001788.6	c.232C>T	p.Pro78Ser	missense_variant	4/14	ENST00000350320.11	NP_001779.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN7	ENST00000350320.11	c.232C>T	p.Pro78Ser	missense_variant	4/14	5	NM_001788.6	ENSP00000344868.8
SEPTIN7	ENST00000635047.1	c.73C>T	p.Pro25Ser	missense_variant	4/7	4		ENSP00000489480.1
SEPTIN7	ENST00000635175.1	n.*149C>T		non_coding_transcript_exon_variant	4/14	2		ENSP00000489192.1
SEPTIN7	ENST00000635175.1	n.*149C>T		3_prime_UTR_variant	4/14	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

GnomAD3 exomes AF: 0.000287 AC: 66 AN: 229666 Hom.: 0 AF XY: 0.000260 AC XY: 33 AN XY: 126836

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 SAS exome AF: 0.0000996

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

Gnomad4 AFR exome AF: 0.0000302

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000840

Gnomad4 OTH exome AF: 0.000519

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

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

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
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

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

LitVar

Other links and lift over

dbSNP: rs199739906; hg19: chr7-35903224;