7-41960988-A-AT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000168.6(GLI3):c.*3341_*3342insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,934 control chromosomes in the GnomAD database, including 1,527 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1523 hom., cov: 30)
  • Exomes 𝑓: 0.16 (4 hom.)
• Consequence: GLI3 NM_000168.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.849

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 -16 ACMG points.

• BP6: Variant 7-41960988-A-AT is Benign according to our data. Variant chr7-41960988-A-AT is described in ClinVar as [Benign]. Clinvar id is 360156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.*3341_*3342insA		3_prime_UTR_variant	15/15	ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.*3341_*3342insA		3_prime_UTR_variant	15/15	5	NM_000168.6	P1
GLI3	ENST00000677288.1	c.*3341_*3342insA		3_prime_UTR_variant	14/14
GLI3	ENST00000677605.1	c.*3341_*3342insA		3_prime_UTR_variant	15/15			P1
GLI3	ENST00000678429.1	c.*3341_*3342insA		3_prime_UTR_variant	15/15			P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18577 AN: 151382 Hom.: 1521 Cov.: 30

Gnomad AFR AF: 0.0329

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.162 AC: 70 AN: 432 Hom.: 4 Cov.: 0 AF XY: 0.173 AC XY: 45 AN XY: 260

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.123 AC: 18572 AN: 151502 Hom.: 1523 Cov.: 30 AF XY: 0.122 AC XY: 9062 AN XY: 74004

Gnomad4 AFR AF: 0.0328

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0673

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.102

Bravo AF: 0.106

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Greig cephalopolysyndactyly syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Pallister-Hall syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs138425063; hg19: chr7-42000586;