7-42134997-T-G

Variant names:

• chr7-42134997-T-G
• rs6974655
• NM_000168.6:c.367+13229A>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000168.6(GLI3):​c.367+13229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 151,980 control chromosomes in the GnomAD database, including 41,281 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (41281 hom., cov: 31)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67

Genes affected

GLI3 (HGNC:4319): (GLI family zinc finger 3) This gene encodes a protein which belongs to the C2H2-type zinc finger proteins subclass of the Gli family. They are characterized as DNA-binding transcription factors and are mediators of Sonic hedgehog (Shh) signaling. The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI3	NM_000168.6	c.367+13229A>C		intron_variant	Intron 3 of 14	ENST00000395925.8	NP_000159.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI3	ENST00000395925.8	c.367+13229A>C		intron_variant	Intron 3 of 14	5	NM_000168.6	ENSP00000379258.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111795 AN: 151862 Hom.: 41250 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.755

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.736 AC: 111879 AN: 151980 Hom.: 41281 Cov.: 31 AF XY: 0.739 AC XY: 54909 AN XY: 74298

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.813

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.756

Alfa AF: 0.731 Hom.: 54843

Bravo AF: 0.739

Asia WGS AF: 0.775 AC: 2696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Benign	0.89

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: rs6974655; hg19: chr7-42174596;