chr1-27822255-A-G

Position:

• chr1-27822255-A-G

Variant summary

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

The NM_177424.3(STX12):​c.757A>G​(p.Ile253Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: STX12 NM_177424.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

Genes affected

STX12 (HGNC:11430): (syntaxin 12) Predicted to enable SNAP receptor activity and SNARE binding activity. Involved in autophagosome assembly; cholesterol efflux; and protein stabilization. Located in several cellular components, including membrane raft; phagocytic vesicle; and phagophore assembly site. Part of SNARE complex. Colocalizes with BLOC-1 complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18267697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX12	NM_177424.3	c.757A>G	p.Ile253Val	missense_variant	9/9	ENST00000373943.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX12	ENST00000373943.9	c.757A>G	p.Ile253Val	missense_variant	9/9	1	NM_177424.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251408 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460880 Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 726832

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: 0.0000187

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.87	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.14
Sift	Benign	0.045	D
Sift4G	Benign	0.19	T
Polyphen		0.064	B
Vest4		0.29
MutPred		0.38		Gain of sheet (P = 0.0827);
MVP		0.18
MPC		0.26
ClinPred		0.35	T
GERP RS		5.6
Varity_R		0.087
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1193434137; hg19: chr1-28148766;