rs3810817

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032575.3(GLIS2):c.1311A>C(p.Ala437Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,548,916 control chromosomes in the GnomAD database, including 25,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 8723 hom., cov: 34)

Exomes 𝑓: 0.14 ( 17187 hom. )

Consequence

GLIS2
NM_032575.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.578

Variant links:

Genes affected

GLIS2 (HGNC:29450): (GLIS family zinc finger 2) This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein's C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120. Mutations in this gene cause nephronophthisis (NPHP), an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys.[provided by RefSeq, Jan 2010]

GLIS2 links:

PAM16 (HGNC:29679): (presequence translocase associated motor 16) This gene encodes a mitochondrial protein involved in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling. This protein also plays a role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix and may be important in reactive oxygen species (ROS) homeostasis. Mutations in this gene cause Megarbane-Dagher-Melike type spondylometaphyseal dysplasia, an early lethal skeletal dysplasia characterized by short stature, developmental delay and other skeletal abnormalities. [provided by RefSeq, May 2017]

PAM16 links:

ENSG00000262712 (HGNC:):

ENSG00000262712 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-4337260-A-C is Benign according to our data. Variant chr16-4337260-A-C is described in ClinVar as [Benign]. Clinvar id is 96223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.578 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLIS2	NM_032575.3 link	c.1311A>C	p.Ala437Ala	synonymous_variant	7/7	ENST00000433375.2	NP_115964.2	Q9BZE0
GLIS2	NM_001318918.2 link	c.1311A>C	p.Ala437Ala	synonymous_variant	8/8		NP_001305847.1	Q9BZE0B3KTH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLIS2	ENST00000433375.2 link	c.1311A>C	p.Ala437Ala	synonymous_variant	7/7	1	NM_032575.3	ENSP00000395547.1	Q9BZE0
GLIS2	ENST00000262366.7 link	c.1311A>C	p.Ala437Ala	synonymous_variant	8/8	2		ENSP00000262366.3	Q9BZE0
PAM16	ENST00000577031.5 link	c.291+3660T>G		intron_variant		4		ENSP00000459113.1	I3L1U7
ENSG00000262712	ENST00000574705.1 link	n.559T>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40545

AN:

152032

Hom.:

8688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.594

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.169

AC:

24801

AN:

146618

Hom.:

2955

AF XY:

0.161

AC XY:

12713

AN XY:

79060

show subpopulations

Gnomad AFR exome

AF:

0.606

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.135

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.136

AC:

189485

AN:

1396766

Hom.:

17187

Cov.:

AF XY:

0.135

AC XY:

92841

AN XY:

689258

show subpopulations

Gnomad4 AFR exome

AF:

0.605

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.153

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.267

AC:

40633

AN:

152150

Hom.:

8723

Cov.:

AF XY:

0.265

AC XY:

19730

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.594

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.120

Hom.:

499

Bravo

AF:

0.289

Asia WGS

AF:

0.191

AC:

666

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 05, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Nephronophthisis 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.0

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over