chr7-41961971-TA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000168.6(GLI3):​c.*2358del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 136,184 control chromosomes in the GnomAD database, including 65 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.030 ( 65 hom., cov: 32)
Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

GLI3
NM_000168.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: -0.972
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1
GnomAdExome4 highest population allele frequency = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLI3NM_000168.6 linkuse as main transcriptc.*2358del 3_prime_UTR_variant 15/15 ENST00000395925.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLI3ENST00000395925.8 linkuse as main transcriptc.*2358del 3_prime_UTR_variant 15/155 NM_000168.6 P1
GLI3ENST00000677288.1 linkuse as main transcriptc.*2358del 3_prime_UTR_variant 14/14
GLI3ENST00000677605.1 linkuse as main transcriptc.*2358del 3_prime_UTR_variant 15/15 P1
GLI3ENST00000678429.1 linkuse as main transcriptc.*2358del 3_prime_UTR_variant 15/15 P1

Frequencies

GnomAD3 genomes
AF:
0.0301
AC:
4097
AN:
136108
Hom.:
65
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0203
Gnomad AMI
AF:
0.0133
Gnomad AMR
AF:
0.0201
Gnomad ASJ
AF:
0.0380
Gnomad EAS
AF:
0.00313
Gnomad SAS
AF:
0.0102
Gnomad FIN
AF:
0.0511
Gnomad MID
AF:
0.0140
Gnomad NFE
AF:
0.0389
Gnomad OTH
AF:
0.0243
GnomAD4 exome
AF:
0.167
AC:
1
AN:
6
Hom.:
0
Cov.:
0
AF XY:
0.167
AC XY:
1
AN XY:
6
show subpopulations
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.500
GnomAD4 genome
AF:
0.0301
AC:
4101
AN:
136178
Hom.:
65
Cov.:
32
AF XY:
0.0302
AC XY:
1987
AN XY:
65780
show subpopulations
Gnomad4 AFR
AF:
0.0203
Gnomad4 AMR
AF:
0.0200
Gnomad4 ASJ
AF:
0.0380
Gnomad4 EAS
AF:
0.00335
Gnomad4 SAS
AF:
0.0104
Gnomad4 FIN
AF:
0.0511
Gnomad4 NFE
AF:
0.0389
Gnomad4 OTH
AF:
0.0241
Bravo
AF:
0.0250

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Greig cephalopolysyndactyly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Polydactyly Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Pallister-Hall syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 12, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144064690; hg19: chr7-42001569; API