7-42113257-G-A

Variant names:

• chr7-42113257-G-A
• rs6463089
• NM_000168.6:c.367+34969C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000168.6(GLI3):​c.367+34969C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 508,554 control chromosomes in the GnomAD database, including 2,255 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 0.11 (922 hom., cov: 31)
  • Exomes 𝑓: 0.082 (1333 hom.)
• Consequence: GLI3 NM_000168.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 10 publications found

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]

HMGN2P30 (HGNC:39397): (high mobility group nucleosomal binding domain 2 pseudogene 30)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000168.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI3	NM_000168.6	MANE Select	c.367+34969C>T		intron	N/A	NP_000159.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI3	ENST00000395925.8	TSL:5 MANE Select	c.367+34969C>T		intron	N/A	ENSP00000379258.3
	GLI3	ENST00000677605.1		c.367+34969C>T		intron	N/A	ENSP00000503743.1
	GLI3	ENST00000678429.1		c.367+34969C>T		intron	N/A	ENSP00000502957.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16038 AN: 151994 Hom.: 921 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0894

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0821 AC: 29258 AN: 356442 Hom.: 1333 AF XY: 0.0796 AC XY: 15900 AN XY: 199802

African (AFR) AF: 0.158 AC: 1594 AN: 10072

American (AMR) AF: 0.0621 AC: 1651 AN: 26568

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 804 AN: 12076

East Asian (EAS) AF: 0.0116 AC: 163 AN: 14064

South Asian (SAS) AF: 0.0525 AC: 3042 AN: 57974

European-Finnish (FIN) AF: 0.0910 AC: 1635 AN: 17964

Middle Eastern (MID) AF: 0.0793 AC: 170 AN: 2144

European-Non Finnish (NFE) AF: 0.0938 AC: 18522 AN: 197358

Other (OTH) AF: 0.0920 AC: 1677 AN: 18222

GnomAD4 genome AF: 0.106 AC: 16058 AN: 152112 Hom.: 922 Cov.: 31 AF XY: 0.101 AC XY: 7534 AN XY: 74364

African (AFR) AF: 0.158 AC: 6573 AN: 41474

American (AMR) AF: 0.0847 AC: 1295 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3468

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5178

South Asian (SAS) AF: 0.0561 AC: 269 AN: 4794

European-Finnish (FIN) AF: 0.0894 AC: 947 AN: 10598

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6363 AN: 68006

Other (OTH) AF: 0.106 AC: 223 AN: 2108

Alfa AF: 0.0992 Hom.: 2307

Bravo AF: 0.109

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.89
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6463089; hg19: chr7-42152856; COSMIC: COSV67894337; COSMIC: COSV67894337;