rs10511455

chr9-4064988-G-C

Variant summary

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

The NM_001042413.2(GLIS3):c.1710+52780C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0587 in 152,208 control chromosomes in the GnomAD database, including 628 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 0.059 (628 hom., cov: 32)
• Consequence: GLIS3 NM_001042413.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS3	NM_001042413.2	c.1710+52780C>G		intron_variant		ENST00000381971.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLIS3	ENST00000381971.8	c.1710+52780C>G		intron_variant		5	NM_001042413.2	P1

Frequencies

GnomAD3 genomes AF: 0.0585 AC: 8903 AN: 152090 Hom.: 620 Cov.: 32

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0587 AC: 8935 AN: 152208 Hom.: 628 Cov.: 32 AF XY: 0.0622 AC XY: 4626 AN XY: 74414

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.0629

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00554

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0311 Hom.: 36

Bravo AF: 0.0731

Asia WGS AF: 0.143 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.6
Dann	Benign	0.54

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: rs10511455; hg19: chr9-4064988;