9-3824894-CTTT-CTT

Variant names:

• chr9-3824894-CT-C
• rs202118987
• NM_001042413.2:c.*3377delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001042413.2(GLIS3):​c.*3377delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 119,988 control chromosomes in the GnomAD database, including 1,347 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1347 hom., cov: 23)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: GLIS3 NM_001042413.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.373
• Publications: 0 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: Ambry Genetics, Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Tourette syndrome

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-3824894-CT-C is Benign according to our data. Variant chr9-3824894-CT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 366887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042413.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS3	NM_001042413.2	MANE Select	c.*3377delA		3_prime_UTR	Exon 11 of 11	NP_001035878.1	Q8NEA6-2
	GLIS3	NM_001438906.1		c.*3377delA		3_prime_UTR	Exon 11 of 11	NP_001425835.1
	GLIS3	NM_001438907.1		c.*3377delA		3_prime_UTR	Exon 11 of 11	NP_001425836.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS3	ENST00000381971.8	TSL:5 MANE Select	c.*3377delA		3_prime_UTR	Exon 11 of 11	ENSP00000371398.3	Q8NEA6-2
	GLIS3	ENST00000324333.14	TSL:1	c.*3377delA		3_prime_UTR	Exon 10 of 10	ENSP00000325494.10	Q8NEA6-1
	GLIS3	ENST00000491889.6	TSL:1	n.*5533delA		non_coding_transcript_exon	Exon 10 of 10	ENSP00000419914.1	F8WEV9

Frequencies

GnomAD3 genomes AF: 0.163 AC: 19543 AN: 119956 Hom.: 1346 Cov.: 23

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.143 AC: 4 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.143 AC XY: 2 AN XY: 14

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) AF: 0.143 AC: 4 AN: 28

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.163 AC: 19538 AN: 119960 Hom.: 1347 Cov.: 23 AF XY: 0.166 AC XY: 9378 AN XY: 56660

African (AFR) AF: 0.172 AC: 5344 AN: 31142

American (AMR) AF: 0.158 AC: 1731 AN: 10964

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 501 AN: 3064

East Asian (EAS) AF: 0.191 AC: 803 AN: 4208

South Asian (SAS) AF: 0.158 AC: 587 AN: 3716

European-Finnish (FIN) AF: 0.190 AC: 975 AN: 5140

Middle Eastern (MID) AF: 0.117 AC: 26 AN: 222

European-Non Finnish (NFE) AF: 0.156 AC: 9211 AN: 59116

Other (OTH) AF: 0.157 AC: 252 AN: 1608

Alfa AF: 0.0325 Hom.: 22

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Neonatal diabetes mellitus with congenital hypothyroidism (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37
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: rs202118987; hg19: chr9-3824894; COSMIC: COSV60925567; COSMIC: COSV60925567;