rs28449480

Variant names:

• chr16-4332270-G-A
• rs28449480
• NM_032575.3:c.-11G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-4332270-G-A
• chr16-4332270-G-C
• chr16-4332270-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032575.3(GLIS2):​c.-11G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,610,762 control chromosomes in the GnomAD database, including 1,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (681 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (625 hom.)
• Consequence: GLIS2 NM_032575.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.508
• Publications: 2 publications found

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]

PAM16 Gene-Disease associations (from GenCC):

• autosomal recessive spondylometaphyseal dysplasia, Megarbane type

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 16-4332270-G-A is Benign according to our data. Variant chr16-4332270-G-A is described in ClinVar as Benign. ClinVar VariationId is 262084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032575.3. 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
	GLIS2	NM_032575.3	MANE Select	c.-11G>A		5_prime_UTR	Exon 2 of 7	NP_115964.2
	GLIS2	NM_001318918.2		c.-11G>A		5_prime_UTR	Exon 3 of 8	NP_001305847.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLIS2	ENST00000433375.2	TSL:1 MANE Select	c.-11G>A		5_prime_UTR	Exon 2 of 7	ENSP00000395547.1
	GLIS2	ENST00000886081.1		c.-11G>A		5_prime_UTR	Exon 2 of 7	ENSP00000556140.1
	GLIS2	ENST00000927239.1		c.-11G>A		5_prime_UTR	Exon 2 of 7	ENSP00000597298.1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7924 AN: 152050 Hom.: 681 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.0408

GnomAD2 exomes AF: 0.0142 AC: 3461 AN: 243058 AF XY: 0.0107

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00751

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000876

Gnomad OTH exome AF: 0.00792

GnomAD4 exome AF: 0.00591 AC: 8623 AN: 1458596 Hom.: 625 Cov.: 32 AF XY: 0.00530 AC XY: 3844 AN XY: 725422

African (AFR) AF: 0.182 AC: 6096 AN: 33420

American (AMR) AF: 0.0121 AC: 538 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.00791 AC: 206 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39616

South Asian (SAS) AF: 0.00115 AC: 99 AN: 85890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51776

Middle Eastern (MID) AF: 0.0115 AC: 66 AN: 5764

European-Non Finnish (NFE) AF: 0.000702 AC: 780 AN: 1111304

Other (OTH) AF: 0.0139 AC: 838 AN: 60272

GnomAD4 genome AF: 0.0522 AC: 7940 AN: 152166 Hom.: 681 Cov.: 32 AF XY: 0.0508 AC XY: 3784 AN XY: 74416

African (AFR) AF: 0.180 AC: 7457 AN: 41442

American (AMR) AF: 0.0189 AC: 289 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68016

Other (OTH) AF: 0.0404 AC: 85 AN: 2106

Alfa AF: 0.0370 Hom.: 76

Bravo AF: 0.0598

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Nephronophthisis 7 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.3
DANN	Benign	0.88
PhyloP100		-0.51
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28449480; hg19: chr16-4382271;