NM_001788.6:c.1212C>T

Variant names:

• chr7-35903153-C-T
• rs2710800
• NM_001788.6:c.1212C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001788.6(SEPTIN7):​c.1212C>T​(p.Phe404Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 152,064 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (71 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (265 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEPTIN7 NM_001788.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.68
• Publications: 3 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 7-35903153-C-T is Benign according to our data. Variant chr7-35903153-C-T is described in ClinVar as [Benign]. Clinvar id is 769709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPTIN7	NM_001788.6	c.1212C>T	p.Phe404Phe	synonymous_variant	Exon 13 of 14	ENST00000350320.11	NP_001779.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPTIN7	ENST00000350320.11	c.1212C>T	p.Phe404Phe	synonymous_variant	Exon 13 of 14	5	NM_001788.6	ENSP00000344868.8
SEPTIN7	ENST00000635175.1	n.*1129C>T		non_coding_transcript_exon_variant	Exon 13 of 14	2		ENSP00000489192.1
SEPTIN7	ENST00000635175.1	n.*1129C>T		3_prime_UTR_variant	Exon 13 of 14	2		ENSP00000489192.1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2471 AN: 151946 Hom.: 67 Cov.: 31

Gnomad AFR AF: 0.00411

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0628

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.00872

Gnomad FIN AF: 0.00284

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0149

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00628 AC: 1453 AN: 231458 AF XY: 0.00557

Gnomad AFR exome AF: 0.00102

Gnomad AMR exome AF: 0.0318

Gnomad ASJ exome AF: 0.000916

Gnomad EAS exome AF: 0.0141

Gnomad FIN exome AF: 0.0000945

Gnomad NFE exome AF: 0.00236

Gnomad OTH exome AF: 0.00492

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00569 AC: 8122 AN: 1427568 Hom.: 265 Cov.: 30 AF XY: 0.00565 AC XY: 4014 AN XY: 710380

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00171 AC: 57 AN: 33298

American (AMR) AF: 0.0442 AC: 1683 AN: 38118

Ashkenazi Jewish (ASJ) AF: 0.00213 AC: 55 AN: 25882

East Asian (EAS) AF: 0.0404 AC: 1571 AN: 38906

South Asian (SAS) AF: 0.00245 AC: 206 AN: 84158

European-Finnish (FIN) AF: 0.00244 AC: 129 AN: 52950

Middle Eastern (MID) AF: 0.00279 AC: 16 AN: 5732

European-Non Finnish (NFE) AF: 0.00369 AC: 4017 AN: 1089056

Other (OTH) AF: 0.00652 AC: 388 AN: 59468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0163 AC: 2479 AN: 152064 Hom.: 71 Cov.: 31 AF XY: 0.0159 AC XY: 1180 AN XY: 74320

African (AFR) AF: 0.00410 AC: 170 AN: 41506

American (AMR) AF: 0.0632 AC: 963 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.0404 AC: 209 AN: 5176

South Asian (SAS) AF: 0.00872 AC: 42 AN: 4814

European-Finnish (FIN) AF: 0.00284 AC: 30 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0149 AC: 1016 AN: 67976

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00992 Hom.: 6

Bravo AF: 0.0241

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2710800; hg19: chr7-35942763; COSMIC: COSV63254129; COSMIC: COSV63254129;