rs10116901

Variant names:

• chr9-3826440-T-C
• rs10116901
• ENST00000491889.6:n.*3988A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-3826440-T-C
• chr9-3826440-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000491889.6(GLIS3):​n.*3988A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 142,114 control chromosomes in the GnomAD database, including 804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (804 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: GLIS3 ENST00000491889.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01
• Publications: 4 publications found

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]

GLIS3 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus with congenital hypothyroidism

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-3826440-T-C is Benign according to our data. Variant chr9-3826440-T-C is described in ClinVar as Benign. ClinVar VariationId is 366925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000491889.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS3	NM_001042413.2	MANE Select	c.*1832A>G		3_prime_UTR	Exon 11 of 11	NP_001035878.1
	GLIS3	NM_001438906.1		c.*1832A>G		3_prime_UTR	Exon 11 of 11	NP_001425835.1
	GLIS3	NM_001438907.1		c.*1832A>G		3_prime_UTR	Exon 11 of 11	NP_001425836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS3	ENST00000491889.6	TSL:1	n.*3988A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000419914.1
	GLIS3	ENST00000381971.8	TSL:5 MANE Select	c.*1832A>G		3_prime_UTR	Exon 11 of 11	ENSP00000371398.3
	GLIS3	ENST00000324333.14	TSL:1	c.*1832A>G		3_prime_UTR	Exon 10 of 10	ENSP00000325494.10

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 13381 AN: 142000 Hom.: 802 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0654

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.000644

Gnomad SAS AF: 0.0237

Gnomad FIN AF: 0.0763

Gnomad MID AF: 0.0592

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.0799

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0944 AC: 13409 AN: 142114 Hom.: 804 Cov.: 33 AF XY: 0.0935 AC XY: 6421 AN XY: 68644

African (AFR) AF: 0.177 AC: 6885 AN: 38832

American (AMR) AF: 0.0662 AC: 895 AN: 13528

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 142 AN: 3356

East Asian (EAS) AF: 0.000645 AC: 3 AN: 4650

South Asian (SAS) AF: 0.0234 AC: 92 AN: 3924

European-Finnish (FIN) AF: 0.0763 AC: 715 AN: 9372

Middle Eastern (MID) AF: 0.0493 AC: 14 AN: 284

European-Non Finnish (NFE) AF: 0.0681 AC: 4457 AN: 65412

Other (OTH) AF: 0.0791 AC: 149 AN: 1884

Alfa AF: 0.00841 Hom.: 465

Bravo AF: 0.0924

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neonatal diabetes mellitus with congenital hypothyroidism (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.66
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10116901; hg19: chr9-3826440;