Variant 16-4332606-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032575.3(GLIS2):c.172+154T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,154 control chromosomes in the GnomAD database, including 16,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 16115 hom., cov: 33)

Consequence

GLIS2
NM_032575.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.486

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-4332606-T-G is Benign according to our data. Variant chr16-4332606-T-G is described in ClinVar as [Benign]. Clinvar id is 1222950.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLIS2	NM_032575.3 linkuse as main transcript	c.172+154T>G		intron_variant		ENST00000433375.2
GLIS2	NM_001318918.2 linkuse as main transcript	c.172+154T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GLIS2	ENST00000433375.2 linkuse as main transcript	c.172+154T>G	intron_variant	1	NM_032575.3	P1
GLIS2	ENST00000262366.7 linkuse as main transcript	c.172+154T>G	intron_variant	2		P1
PAM16	ENST00000577031.5 linkuse as main transcript	c.292-832A>C	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61068

AN:

152036

Hom.:

16056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.743

Gnomad AMI

AF:

0.240

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.371

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

GnomAD4 genome

AF:

0.402

AC:

61190

AN:

152154

Hom.:

16115

Cov.:

AF XY:

0.405

AC XY:

30144

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.743

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.216

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.267

Hom.:

8205

Bravo

AF:

0.423

Asia WGS

AF:

0.459

AC:

1595

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.5

DANN

Benign

0.47

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