7-41961971-T-TA

Position:

• chr7-41961971-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000168.6(GLI3):​c.*2358_*2359insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00887 in 136,436 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLI3 NM_000168.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.972

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.

• BP6: Variant 7-41961971-T-TA is Benign according to our data. Variant chr7-41961971-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 1321545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00887 (1210/136436) while in subpopulation AFR AF= 0.0211 (782/37080). AF 95% confidence interval is 0.0199. There are 12 homozygotes in gnomad4. There are 525 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1210 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI3	NM_000168.6	c.*2358_*2359insT		3_prime_UTR_variant	15/15	ENST00000395925.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI3	ENST00000395925.8	c.*2358_*2359insT		3_prime_UTR_variant	15/15	5	NM_000168.6	P1
GLI3	ENST00000677288.1	c.*2358_*2359insT		3_prime_UTR_variant	14/14
GLI3	ENST00000677605.1	c.*2358_*2359insT		3_prime_UTR_variant	15/15			P1
GLI3	ENST00000678429.1	c.*2358_*2359insT		3_prime_UTR_variant	15/15			P1

Frequencies

GnomAD3 genomes AF: 0.00875 AC: 1193 AN: 136360 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00660

Gnomad ASJ AF: 0.000620

Gnomad EAS AF: 0.000416

Gnomad SAS AF: 0.000708

Gnomad FIN AF: 0.000605

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00487

Gnomad OTH AF: 0.0116

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00887 AC: 1210 AN: 136436 Hom.: 12 Cov.: 32 AF XY: 0.00796 AC XY: 525 AN XY: 65952

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00659

Gnomad4 ASJ AF: 0.000620

Gnomad4 EAS AF: 0.000418

Gnomad4 SAS AF: 0.000710

Gnomad4 FIN AF: 0.000605

Gnomad4 NFE AF: 0.00487

Gnomad4 OTH AF: 0.0120

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs144064690; hg19: chr7-42001569;