16-4777919-G-C

Position:

• chr16-4777919-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144605.5(SEPTIN12):​c.955C>G​(p.His319Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SEPTIN12 NM_144605.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

Genes affected

SEPTIN12 (HGNC:26348): (septin 12) This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ENSG00000285952 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17895323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEPTIN12	NM_144605.5	c.955C>G	p.His319Asp	missense_variant	10/10	ENST00000268231.13	NP_653206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEPTIN12	ENST00000268231.13	c.955C>G	p.His319Asp	missense_variant	10/10	1	NM_144605.5	ENSP00000268231.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453100 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722108

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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

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

Jul 12, 2023

The c.955C>G (p.H319D) alteration is located in exon 10 (coding exon 9) of the SEPT12 gene. This alteration results from a C to G substitution at nucleotide position 955, causing the histidine (H) at amino acid position 319 to be replaced by an aspartic acid (D). 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	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	.;T
Eigen	Benign	-0.080
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.96	N;N
REVEL	Benign	0.12
Sift	Benign	0.50	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.57	P;P
Vest4		0.36
MutPred		0.50		.;Gain of loop (P = 0.0166);
MVP		0.50
MPC		0.026
ClinPred		0.44	T
GERP RS		3.6
Varity_R		0.57
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-4827920;