9-3946659-T-C

Position:

• chr9-3946659-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042413.2(GLIS3):​c.1711-9470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,096 control chromosomes in the GnomAD database, including 3,735 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 0.22 (3735 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

Genes affected

GLIS3 (HGNC:28510): (GLIS family zinc finger 3) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear protein with five C2H2-type zinc finger domains. This protein functions as both a repressor and activator of transcription and is specifically involved in the development of pancreatic beta cells, the thyroid, eye, liver and kidney. Mutations in this gene have been associated with neonatal diabetes and congenital hypothyroidism (NDH). Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only two have been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS3	NM_001042413.2	c.1711-9470A>G		intron_variant		ENST00000381971.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIS3	ENST00000381971.8	c.1711-9470A>G		intron_variant		5	NM_001042413.2	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33012 AN: 151978 Hom.: 3712 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.217 AC: 33069 AN: 152096 Hom.: 3735 Cov.: 32 AF XY: 0.220 AC XY: 16389 AN XY: 74358

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.223

Alfa AF: 0.212 Hom.: 2198

Bravo AF: 0.210

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.017
DANN	Benign	0.50

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: rs10491899; hg19: chr9-3946659;