12-57471538-G-T

Position:

• chr12-57471538-G-T

Variant summary

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

The NM_005269.3(GLI1):​c.2798G>T​(p.Gly933Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G933D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLI1 NM_005269.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925

Genes affected

GLI1 (HGNC:4317): (GLI family zinc finger 1) This gene encodes a member of the Kruppel family of zinc finger proteins. The encoded transcription factor is activated by the sonic hedgehog signal transduction cascade and regulates stem cell proliferation. The activity and nuclear localization of this protein is negatively regulated by p53 in an inhibitory loop. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

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=0.23080164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI1	NM_005269.3	c.2798G>T	p.Gly933Val	missense_variant	12/12	ENST00000228682.7	NP_005260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI1	ENST00000228682.7	c.2798G>T	p.Gly933Val	missense_variant	12/12	1	NM_005269.3	ENSP00000228682.2
GLI1	ENST00000528467.1	c.2675G>T	p.Gly892Val	missense_variant	10/10	1		ENSP00000434408.1
GLI1	ENST00000546141.5	c.2675G>T	p.Gly892Val	missense_variant	11/11	5		ENSP00000441006.1
GLI1	ENST00000543426.5	c.2414G>T	p.Gly805Val	missense_variant	10/10	5		ENSP00000437607.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460710 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 726654

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.34	.;T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.76	T;T;T;.
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	.;N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.52	N;N;N;N
REVEL	Benign	0.044
Sift	Uncertain	0.0090	D;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.44	.;B;.;.
Vest4		0.10
MutPred		0.25		.;Gain of catalytic residue at P928 (P = 0.0113);.;.;
MVP		0.52
MPC		0.37
ClinPred		0.24	T
GERP RS		0.56
Varity_R		0.072
gMVP		0.39

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: rs2228224; hg19: chr12-57865321;