chr7-55807216-A-G

Position:

• chr7-55807216-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_207366.3(SEPTIN14):​c.860T>C​(p.Met287Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SEPTIN14 NM_207366.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

Genes affected

SEPTIN14 (HGNC:33280): (septin 14) SEPT14 is a member of the highly conserved septin family of GTP-binding cytoskeletal proteins implicated in membrane transport, apoptosis, cell polarity, cell cycle regulation, cytokinesis, and other cellular functions (Peterson et al., 2007 [PubMed 17922164]).[supplied by OMIM, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPTIN14	NM_207366.3	c.860T>C	p.Met287Thr	missense_variant	8/10	ENST00000388975.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPTIN14	ENST00000388975.4	c.860T>C	p.Met287Thr	missense_variant	8/10	2	NM_207366.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451574 Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 2 AN XY: 721870

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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 09, 2022

The c.860T>C (p.M287T) alteration is located in exon 8 (coding exon 7) of the SEPT14 gene. This alteration results from a T to C substitution at nucleotide position 860, causing the methionine (M) at amino acid position 287 to be replaced by a threonine (T). 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	0.21
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.074	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.047	D
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	0.79	D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.039	D
Polyphen		0.20	B
Vest4		0.76
MutPred		0.72		Loss of stability (P = 0.017);
MVP		0.80
MPC		0.089
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.47
gMVP		0.70

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: rs1214859190; hg19: chr7-55874909;