16-4332606-T-G

Position:

• chr16-4332606-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.486

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]

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]

ACMG classification

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	Protein	UniProt
GLIS2	NM_032575.3	c.172+154T>G		intron_variant		ENST00000433375.2	NP_115964.2
GLIS2	NM_001318918.2	c.172+154T>G		intron_variant			NP_001305847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLIS2	ENST00000433375.2	c.172+154T>G		intron_variant		1	NM_032575.3	ENSP00000395547.1
GLIS2	ENST00000262366.7	c.172+154T>G		intron_variant		2		ENSP00000262366.3
PAM16	ENST00000577031.5	c.292-832A>C		intron_variant		4		ENSP00000459113.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61068 AN: 152036 Hom.: 16056 Cov.: 33

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.: 33 AF XY: 0.405 AC XY: 30144 AN XY: 74390

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

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

Other links and lift over

dbSNP: rs9938257; hg19: chr16-4382607; COSMIC: COSV52110168; COSMIC: COSV52110168;