NM_001042413.2:c.*3409G>A

Variant names:

• chr9-3824863-C-T
• rs115222174
• NM_001042413.2:c.*3409G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001042413.2(GLIS3):​c.*3409G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0492 in 142,870 control chromosomes in the GnomAD database, including 554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (554 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLIS3 NM_001042413.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.954
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 9-3824863-C-T is Benign according to our data. Variant chr9-3824863-C-T is described in ClinVar as Benign. ClinVar VariationId is 366886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 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.*3409G>A		3_prime_UTR	Exon 11 of 11	NP_001035878.1	Q8NEA6-2
	GLIS3	NM_001438906.1		c.*3409G>A		3_prime_UTR	Exon 11 of 11	NP_001425835.1
	GLIS3	NM_001438907.1		c.*3409G>A		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.*3409G>A		3_prime_UTR	Exon 11 of 11	ENSP00000371398.3	Q8NEA6-2
	GLIS3	ENST00000324333.14	TSL:1	c.*3409G>A		3_prime_UTR	Exon 10 of 10	ENSP00000325494.10	Q8NEA6-1
	GLIS3	ENST00000491889.6	TSL:1	n.*5565G>A		non_coding_transcript_exon	Exon 10 of 10	ENSP00000419914.1	F8WEV9

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 6999 AN: 142820 Hom.: 553 Cov.: 31

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000669

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.000601

Gnomad OTH AF: 0.0425

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 406 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 250

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: 0.00 AC: 0 AN: 400

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0492 AC: 7023 AN: 142870 Hom.: 554 Cov.: 31 AF XY: 0.0480 AC XY: 3301 AN XY: 68838

African (AFR) AF: 0.172 AC: 6620 AN: 38526

American (AMR) AF: 0.0196 AC: 268 AN: 13680

Ashkenazi Jewish (ASJ) AF: 0.000292 AC: 1 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4836

South Asian (SAS) AF: 0.000447 AC: 2 AN: 4472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8308

Middle Eastern (MID) AF: 0.0354 AC: 9 AN: 254

European-Non Finnish (NFE) AF: 0.000602 AC: 40 AN: 66500

Other (OTH) AF: 0.0422 AC: 83 AN: 1966

Alfa AF: 0.0304 Hom.: 115

Bravo AF: 0.0559

Asia WGS AF: 0.0120 AC: 41 AN: 3476

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.95
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: rs115222174; hg19: chr9-3824863;